Hostname: page-component-76fb5796d-x4r87 Total loading time: 0 Render date: 2024-04-26T03:35:50.843Z Has data issue: false hasContentIssue false
  • English
  • Français

Computational approaches for drug discovery against trypanosomatid-caused diseases

Published online by Cambridge University Press:  12 February 2020

Claudio A. Pereira Open the ORCID record for Claudio A. Pereira [Opens in a new window] ,
Melisa Sayé ,
Chantal Reigada ,
Ariel M. Silber ,
Guillermo R. Labadie ,
Mariana R. Miranda  and
Edward Valera-Vera
Claudio A. Pereira*
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Melisa Sayé
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Chantal Reigada
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Ariel M. Silber
Affiliation:
Laboratory of Biochemistry of Tryps – LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Guillermo R. Labadie
Affiliation:
Instituto de Química Rosario (IQUIR-CONICET), Universidad Nacional de Rosario, Rosario, Argentina Departamento de Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
Mariana R. Miranda
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Edward Valera-Vera
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
*
Author for correspondence: Claudio A. Pereira, E-mail: cpereira@retina.ar
Get access Rights & Permissions [Opens in a new window]

Abstract

During three decades, only about 20 new drugs have been developed for malaria, tuberculosis and all neglected tropical diseases (NTDs). This critical situation was reached because NTDs represent only 10% of health research investments; however, they comprise about 90% of the global disease burden. Computational simulations applied in virtual screening (VS) strategies are very efficient tools to identify pharmacologically active compounds or new indications for drugs already administered for other diseases. One of the advantages of this approach is the low time-consuming and low-budget first stage, which filters for testing experimentally a group of candidate compounds with high chances of binding to the target and present trypanocidal activity. In this work, we review the most common VS strategies that have been used for the identification of new drugs with special emphasis on those applied to trypanosomiasis and leishmaniasis. Computational simulations based on the selected protein targets or their ligands are explained, including the method selection criteria, examples of successful VS campaigns applied to NTDs, a list of validated molecular targets for drug development and repositioned drugs for trypanosomatid-caused diseases. Thereby, here we present the state-of-the-art of VS and drug repurposing to conclude pointing out the future perspectives in the field.

Type
Review Article
Information
Parasitology , Volume 147 , Issue 6 , May 2020 , pp. 611 - 633
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abeloff, MD, Rosen, ST, Luk, GD, Baylin, SB, Zeltzman, M and Sjoerdsma, A (1986) Phase II trials of alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. Cancer Treatment Reports 70, 843–845.Google ScholarPubMed
Abi Hussein, H, Geneix, C, Petitjean, M, Borrel, A, Flatters, D and Camproux, AC (2017) Global vision of druggability issues: applications and perspectives. Drug Discovery Today 22, 404–415.CrossRefGoogle Scholar
Adl, SM, Bass, D, Lane, CE, Lukes, J, Schoch, CL, Smirnov, A, Agatha, S, Berney, C, Brown, MW, Burki, F, Cardenas, P, Cepicka, I, Chistyakova, L, Del Campo, J, Dunthorn, M, Edvardsen, B, Eglit, Y, Guillou, L, Hampl, V, Heiss, AA, Hoppenrath, M, James, TY, Karnkowska, A, Karpov, S, Kim, E, Kolisko, M, Kudryavtsev, A, Lahr, DJG, Lara, E, Le Gall, L, Lynn, DH, Mann, DG, Massana, R, Mitchell, EAD, Morrow, C, Park, JS, Pawlowski, JW, Powell, MJ, Richter, DJ, Rueckert, S, Shadwick, L, Shimano, S, Spiegel, FW, Torruella, G, Youssef, N, Zlatogursky, V and Zhang, Q (2019) Revisions to the classification, nomenclature, and diversity of eukaryotes. Journal of Eukaryotic Microbiology 66, 4–119.Google ScholarPubMed
Aerts, C, Sunyoto, T, Tediosi, F and Sicuri, E (2017) Are public-private partnerships the solution to tackle neglected tropical diseases? A systematic review of the literature. Health Policy 121, 745–754.CrossRefGoogle Scholar
Agnihotri, P, Mishra, AK, Mishra, S, Sirohi, VK, Sahasrabuddhe, AA and Pratap, JV (2017) Identification of novel inhibitors of Leishmania donovani gamma-glutamylcysteine synthetase using structure-based virtual screening, docking, molecular dynamics simulation, and in vitro studies. Journal of Chemical Information and Modeling 57, 815–825.CrossRefGoogle ScholarPubMed
Aidas, K, Angeli, C, Bak, KL, Bakken, V, Bast, R, Boman, L, Christiansen, O, Cimiraglia, R, Coriani, S, Dahle, P, Dalskov, EK, Ekstrom, U, Enevoldsen, T, Eriksen, JJ, Ettenhuber, P, Fernandez, B, Ferrighi, L, Fliegl, H, Frediani, L, Hald, K, Halkier, A, Hattig, C, Heiberg, H, Helgaker, T, Hennum, AC, Hettema, H, Hjertenaes, E, Host, S, Hoyvik, IM, Iozzi, MF, Jansik, B, Jensen, HJ, Jonsson, D, Jorgensen, P, Kauczor, J, Kirpekar, S, Kjaergaard, T, Klopper, W, Knecht, S, Kobayashi, R, Koch, H, Kongsted, J, Krapp, A, Kristensen, K, Ligabue, A, Lutnaes, OB, Melo, JI, Mikkelsen, KV, Myhre, RH, Neiss, C, Nielsen, CB, Norman, P, Olsen, J, Olsen, JM, Osted, A, Packer, MJ, Pawlowski, F, Pedersen, TB, Provasi, PF, Reine, S, Rinkevicius, Z, Ruden, TA, Ruud, K, Rybkin, VV, Salek, P, Samson, CC, de Meras, AS, Saue, T, Sauer, SP, Schimmelpfennig, B, Sneskov, K, Steindal, AH, Sylvester-Hvid, KO, Taylor, PR, Teale, AM, Tellgren, EI, Tew, DP, Thorvaldsen, AJ, Thogersen, L, Vahtras, O, Watson, MA, Wilson, DJ, Ziolkowski, M and Agren, H (2014) The Dalton quantum chemistry program system. Wiley Interdisciplinary Reviews. Computational Molecular Science 4, 269–284.CrossRefGoogle ScholarPubMed
Alberca, LN, Sbaraglini, ML, Balcazar, D, Fraccaroli, L, Carrillo, C, Medeiros, A, Benitez, D, Comini, M and Talevi, A (2016) Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning. Journal of Computer-Aided Molecular Design 30, 305–321.CrossRefGoogle ScholarPubMed
Alberca, LN, Sbaraglini, ML, Morales, JF, Dietrich, R, Ruiz, MD, Pino Martinez, AM, Miranda, CG, Fraccaroli, L, Alba Soto, CD, Carrillo, C, Palestro, PH and Talevi, A (2018) Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake. Frontiers in Cellular and Infection Microbiology 8, 173.CrossRefGoogle ScholarPubMed
Alcântara, LM, Ferreira, TCS, Gadelha, FR and Miguel, DC (2018) Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis. International Journal for Parasitology: Drugs and Drug Resistance 8, 430–439.Google ScholarPubMed
Allen, WJ, Balius, TE, Mukherjee, S, Brozell, SR, Moustakas, DT, Lang, PT, Case, DA, Kuntz, ID and Rizzo, RC (2015) DOCK 6: impact of new features and current docking performance. Journal of Computational Chemistry 36, 1132–1156.CrossRefGoogle ScholarPubMed
Alves, F, Bilbe, G, Blesson, S, Goyal, V, Monnerat, S, Mowbray, C, Muthoni Ouattara, G, Pecoul, B, Rijal, S, Rode, J, Solomos, A, Strub-Wourgaft, N, Wasunna, M, Wells, S, Zijlstra, EE, Arana, B and Alvar, J (2018) Recent development of visceral leishmaniasis treatments: successes, pitfalls, and perspectives. Clinical Microbiology Reviews 31, e00048–18.CrossRefGoogle Scholar
Aronson, NE and Joya, CA (2019) Cutaneous leishmaniasis: updates in diagnosis and management. Infectious Disease Clinics of North America 33, 101–117.CrossRefGoogle ScholarPubMed
Aronson, N, Herwaldt, BL, Libman, M, Pearson, R, Lopez-Velez, R, Weina, P, Carvalho, E, Ephros, M, Jeronimo, S and Magill, A (2017) Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). American Journal of Tropical Medicine and Hygiene 96, 24–45.CrossRefGoogle Scholar
Ashburn, TT and Thor, KB (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nature Reviews. Drug Discovery 3, 673–683.CrossRefGoogle ScholarPubMed
Avilan, L, Gualdron-Lopez, M, Quinones, W, Gonzalez-Gonzalez, L, Hannaert, V, Michels, PA and Concepcion, JL (2011) Enolase: a key player in the metabolism and a probable virulence factor of trypanosomatid parasites-perspectives for its use as a therapeutic target. Enzyme Research 2011, 932549.CrossRefGoogle Scholar
B-Rao, C, Subramanian, J and Sharma, SD (2009) Managing protein flexibility in docking and its applications. Drug Discovery Today 14, 394–400.CrossRefGoogle ScholarPubMed
Babokhov, P, Sanyaolu, AO, Oyibo, WA, Fagbenro-Beyioku, AF and Iriemenam, NC (2013) A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis. Pathogens and Global Health 107, 242–252.CrossRefGoogle ScholarPubMed
Baell, JB and Holloway, GA (2010) New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. Journal of Medicinal Chemistry 53, 2719–2740.CrossRefGoogle ScholarPubMed
Baell, J and Walters, MA (2014) Chemistry: chemical con artists foil drug discovery. Nature 513, 481–483.CrossRefGoogle ScholarPubMed
Bahia, MT, de Andrade, IM, Martins, TA, do Nascimento, AF, Diniz Lde, F, Caldas, IS, Talvani, A, Trunz, BB, Torreele, E and Ribeiro, I (2012) Fexinidazole: a potential new drug candidate for Chagas disease. PLoS Neglected Tropical Diseases 6, e1870.CrossRefGoogle ScholarPubMed
Bajusz, D, Racz, A and Heberger, K (2015) Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations? Journal of Cheminformatics 7, 20.CrossRefGoogle ScholarPubMed
Bakker, BM, Westerhoff, HV, Opperdoes, FR and Michels, PA (2000) Metabolic control analysis of glycolysis in trypanosomes as an approach to improve selectivity and effectiveness of drugs. Molecular and Biochemical Parasitology 106, 1–10.CrossRefGoogle ScholarPubMed
Banegas-Luna, AJ, Ceron-Carrasco, JP and Perez-Sanchez, H (2018) A review of ligand-based virtual screening web tools and screening algorithms in large molecular databases in the age of big data. Future Medicinal Chemistry 10, 2641–2658.CrossRefGoogle ScholarPubMed
Barrett, MP, Mottram, JC and Coombs, GH (1999) Recent advances in identifying and validating drug targets in trypanosomes and leishmanias. Trends in Microbiology 7, 82–88.CrossRefGoogle ScholarPubMed
Batool, M, Ahmad, B and Choi, S (2019) A structure-based drug discovery paradigm. International Journal of Molecular Sciences 20, E2783.CrossRefGoogle ScholarPubMed
Bell, AS, Mills, JE, Williams, GP, Brannigan, JA, Wilkinson, AJ, Parkinson, T, Leatherbarrow, RJ, Tate, EW, Holder, AA and Smith, DF (2012) Selective inhibitors of protozoan protein N-myristoyltransferases as starting points for tropical disease medicinal chemistry programs. PLoS Neglected Tropical Diseases 6, e1625.CrossRefGoogle ScholarPubMed
Bellera, CL, Balcazar, DE, Alberca, L, Labriola, CA, Talevi, A and Carrillo, C (2013) Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects. Journal of Chemical Information and Modeling 53, 2402–2408.CrossRefGoogle ScholarPubMed
Bellera, CL, Balcazar, DE, Alberca, L, Labriola, CA, Talevi, A and Carrillo, C (2014) Identification of levothyroxine antichagasic activity through computer-aided drug repurposing. TheScientificWorldJournal 2014, 279618.CrossRefGoogle ScholarPubMed
Belllera, CL, Sbaraglini, ML, Alberca, LN, Alice, JI and Talevi, A (2019) In silico modeling of FDA-approved drugs for discovery of therapies against neglected diseases: a drug repurposing approach. In Roy, K. (ed.), In Silico Drug Design: Repurposing Techniques and Methodologies. Massachusetts, USA: Academic Press, pp. 625–648.CrossRefGoogle Scholar
Beneke, T, Madden, R, Makin, L, Valli, J, Sunter, J and Gluenz, E (2017) A CRISPR Cas9 high-throughput genome editing toolkit for kinetoplastids. Royal Society Open Science 4, 170095.CrossRefGoogle ScholarPubMed
Benitez, D, Medeiros, A, Fiestas, L, Panozzo-Zenere, EA, Maiwald, F, Prousis, KC, Roussaki, M, Calogeropoulou, T, Detsi, A, Jaeger, T, Sarlauskas, J, Peterlin Masic, L, Kunick, C, Labadie, GR, Flohe, L and Comini, MA (2016) Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids. PLoS Neglected Tropical Diseases 10, e0004617.CrossRefGoogle ScholarPubMed
Benkert, P, Biasini, M and Schwede, T (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics (Oxford, England) 27, 343–350.CrossRefGoogle ScholarPubMed
Berman, HM, Westbrook, J, Feng, Z, Gilliland, G, Bhat, TN, Weissig, H, Shindyalov, IN and Bourne, PE (2000) The protein data bank. Nucleic Acids Research 28, 235–242.CrossRefGoogle ScholarPubMed
Bern, C (2015) Chagas’ disease. New England Journal of Medicine 373, 456–466.CrossRefGoogle ScholarPubMed
Berna, L, Rodriguez, M, Chiribao, ML, Parodi-Talice, A, Pita, S, Rijo, G, Alvarez-Valin, F and Robello, C (2018) Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi. Microbial Genomics 4. doi: 10.1099/mgen.0.000177.CrossRefGoogle ScholarPubMed
Berneman, A, Montout, L, Goyard, S, Chamond, N, Cosson, A, d'Archivio, S, Gouault, N, Uriac, P, Blondel, A and Minoprio, P (2013) Combined approaches for drug design points the way to novel proline racemase inhibitor candidates to fight Chagas’ disease. PLoS ONE 8, e60955.CrossRefGoogle ScholarPubMed
Berriman, M, Ghedin, E, Hertz-Fowler, C, Blandin, G, Renauld, H, Bartholomeu, DC, Lennard, NJ, Caler, E, Hamlin, NE, Haas, B, Bohme, U, Hannick, L, Aslett, MA, Shallom, J, Marcello, L, Hou, L, Wickstead, B, Alsmark, UC, Arrowsmith, C, Atkin, RJ, Barron, AJ, Bringaud, F, Brooks, K, Carrington, M, Cherevach, I, Chillingworth, TJ, Churcher, C, Clark, LN, Corton, CH, Cronin, A, Davies, RM, Doggett, J, Djikeng, A, Feldblyum, T, Field, MC, Fraser, A, Goodhead, I, Hance, Z, Harper, D, Harris, BR, Hauser, H, Hostetler, J, Ivens, A, Jagels, K, Johnson, D, Johnson, J, Jones, K, Kerhornou, AX, Koo, H, Larke, N, Landfear, S, Larkin, C, Leech, V, Line, A, Lord, A, Macleod, A, Mooney, PJ, Moule, S, Martin, DM, Morgan, GW, Mungall, K, Norbertczak, H, Ormond, D, Pai, G, Peacock, CS, Peterson, J, Quail, MA, Rabbinowitsch, E, Rajandream, MA, Reitter, C, Salzberg, SL, Sanders, M, Schobel, S, Sharp, S, Simmonds, M, Simpson, AJ, Tallon, L, Turner, CM, Tait, A, Tivey, AR, Van Aken, S, Walker, D, Wanless, D, Wang, S, White, B, White, O, Whitehead, S, Woodward, J, Wortman, J, Adams, MD, Embley, TM, Gull, K, Ullu, E, Barry, JD, Fairlamb, AH, Opperdoes, F, Barrell, BG, Donelson, JE, Hall, N, Fraser, CM, Melville, SE and El-Sayed, NM (2005) The genome of the African trypanosome Trypanosoma brucei. Science (New York, N.Y.) 309, 416–422.CrossRefGoogle ScholarPubMed
Bhattacharya, A, Wunderlich, Z, Monleon, D, Tejero, R and Montelione, GT (2008) Assessing model accuracy using the homology modeling automatically software. Proteins 70, 105–118.CrossRefGoogle ScholarPubMed
Boscardin, SB, Torrecilhas, AC, Manarin, R, Revelli, S, Rey, EG, Tonelli, RR and Silber, AM (2010) Chagas’ disease: an update on immune mechanisms and therapeutic strategies. Journal of Cellular and Molecular Medicine 14, 1373–1384.CrossRefGoogle ScholarPubMed
Bottieau, E and Clerinx, J (2019) Human African trypanosomiasis: progress and stagnation. Infectious Disease Clinics of North America 33, 61–77.CrossRefGoogle ScholarPubMed
KR, Brimacombe, MJ, Walsh, Liu, L, MG, Vásquez-Valdivieso, HP, Morgan, McNae, I, LA, Fothergill-Gilmore, PAM, Michels, DS, Auld, Simeonov, A, MD, Walkinshaw, Shen, M and MB, Boxer (2017) Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase. ACS Medicinal Chemistry Letters 5, 12–17.Google Scholar
Brown, N and Jacoby, E (2006) On scaffolds and hopping in medicinal chemistry. Mini Reviews in Medicinal Chemistry 6, 1217–1229.CrossRefGoogle ScholarPubMed
Burle-Caldas Gde, A, Grazielle-Silva, V, Laibida, LA, DaRocha, WD and Teixeira, SM (2015) Expanding the tool box for genetic manipulation of Trypanosoma cruzi. Molecular and Biochemical Parasitology 203, 25–33.CrossRefGoogle ScholarPubMed
Burri, C and Brun, R (2003) Eflornithine for the treatment of human African trypanosomiasis. Parasitology Research 90, S49–S52.CrossRefGoogle ScholarPubMed
Burza, S, Croft, SL and Boelaert, M (2018) Leishmaniasis. Lancet (London, England) 392, 951–970.CrossRefGoogle ScholarPubMed
Buscher, P, Cecchi, G, Jamonneau, V and Priotto, G (2017) Human African trypanosomiasis. Lancet (London, England) 390, 2397–2409.CrossRefGoogle ScholarPubMed
Calvet, CM, Choi, JY, Thomas, D, Suzuki, B, Hirata, K, Lostracco-Johnson, S, de Mesquita, LB, Nogueira, A, Meuser-Batista, M, Silva, TA, Siqueira-Neto, JL, Roush, WR, de Souza Pereira, MC, McKerrow, JH and Podust, LM (2017) 4-aminopyridyl-based Lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLoS Neglected Tropical Diseases 11, e0006132.CrossRefGoogle Scholar
Case, DA, Ben-Shalom, IY, Brozell, SR, Cerutti, DS, Cheatham, TE III, Cruzeiro, VWD, Darden, TA, Duke, RE, Ghoreishi, D, Gilson, MK, Gohlke, H, Goetz, AW, Greene, D, Harris, R, Homeyer, N, Huang, Y, Izadi, S, Kovalenko, A, Kurtzman, T, Lee, TS, LeGrand, S, Li, P, Lin, C, Liu, J, Luchko, T, Luo, R, Mermelstein, DJ, Merz, KM, Miao, Y, Monard, G, Nguyen, C, Nguyen, H, Omelyan, I, Onufriev, A, Pan, F, Qi, R, Roe, DR, Roitberg, A, Sagui, C, Schott-Verdugo, S, Shen, J, Simmerling, CL, Smith, J, SalomonFerrer, R, Swails, J, Walker, RC, Wang, J, Wei, H, Wolf, RM, Wu, X, Xiao, L, York, DM and Kollman, PA (2018) AMBER 2018. San Francisco: University of California.Google Scholar
Chagas, C (1909) Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem. Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem 1, 1678–8060.Google Scholar
Chaput, L, Martinez-Sanz, J, Saettel, N and Mouawad, L (2016) Benchmark of four popular virtual screening programs: construction of the active/decoy dataset remains a major determinant of measured performance. Journal of Cheminformatics 8, 56.CrossRefGoogle Scholar
Chatelain, E and Ioset, JR (2011) Drug discovery and development for neglected diseases: the DNDi model. Drug Design, Development and Therapy 5, 175–181.Google ScholarPubMed
Chavez-Fumagalli, MA, Lage, DP, Tavares, GSV, Mendonca, DVC, Dias, DS, Ribeiro, PAF, Ludolf, F, Costa, LE, Coelho, VTS and Coelho, EAF (2019) In silico Leishmania proteome mining applied to identify drug target potential to be used to treat against visceral and tegumentary leishmaniasis. Journal of Molecular Graphics & Modelling 87, 89–97.CrossRefGoogle ScholarPubMed
Cheleski, J, Rocha, JR, Pinheiro, MP, Wiggers, HJ, da Silva, AB, Nonato, MC and Montanari, CA (2010) Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery. European Journal of Medicinal Chemistry 45, 5899–5909.CrossRefGoogle ScholarPubMed
Chibli, LA, Schmidt, TJ, Nonato, MC, Calil, FA and Da Costa, FB (2018) Natural products as inhibitors of Leishmania major dihydroorotate dehydrogenase. European Journal of Medicinal Chemistry 157, 852–866.CrossRefGoogle ScholarPubMed
Choi, JY, Calvet, CM, Gunatilleke, SS, Ruiz, C, Cameron, MD, McKerrow, JH, Podust, LM and Roush, WR (2013) Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-chagas agents. Journal of Medicinal Chemistry 56, 7651–7668.CrossRefGoogle ScholarPubMed
Chong, CR and Sullivan, DJ Jr (2007) New uses for old drugs. Nature 448, 645–646.CrossRefGoogle ScholarPubMed
Croft, SL, Sundar, S and Fairlamb, AH (2006) Drug resistance in leishmaniasis. Clinical Microbiology Reviews 19, 111–126.CrossRefGoogle ScholarPubMed
Czech, T, Lalani, R and Oyewumi, MO (2019) Delivery systems as vital tools in drug repurposing. AAPS PharmSciTech 20, 116.CrossRefGoogle ScholarPubMed
Dahlin, JL, Nissink, JW, Strasser, JM, Francis, S, Higgins, L, Zhou, H, Zhang, Z and Walters, MA (2015) PAINS In the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS. Journal of Medicinal Chemistry 58, 2091–2113.CrossRefGoogle ScholarPubMed
Danishuddin, M and Khan, AU (2016) Descriptors and their selection methods in QSAR analysis: paradigm for drug design. Drug Discovery Today, 21, 1291–1302.CrossRefGoogle ScholarPubMed
DasGupta, D, Kaushik, R and Jayaram, B (2015) From Ramachandran maps to tertiary structures of proteins. Journal of Physical Chemistry B 119, 11136–11145.CrossRefGoogle ScholarPubMed
Dassault Systèmes BIOVIA, (2017). Discovery studio, San Diego: Dassault Systèmes, 2017.Google Scholar
Davidson, RN, den Boer, M and Ritmeijer, K (2009) Paromomycin. Transactions of the Royal Society of Tropical Medicine and Hygiene 103, 653–660.CrossRefGoogle ScholarPubMed
Deeks, ED (2019) Fexinidazole: first global approval. Drugs 79, 215–220.CrossRefGoogle ScholarPubMed
Defelipe, LA, Arcon, JP, Modenutti, CP, Marti, MA, Turjanski, AG and Barril, X (2018) Solvents to fragments to drugs: MD applications in drug design. Molecules 23, E3269.CrossRefGoogle ScholarPubMed
Delavan, B, Roberts, R, Huang, R, Bao, W, Tong, W and Liu, Z (2018) Computational drug repositioning for rare diseases in the era of precision medicine. Drug Discovery Today 23, 382–394.CrossRefGoogle ScholarPubMed
Demir, O, Labaied, M, Merritt, C, Stuart, K and Amaro, RE (2014) Computer-aided discovery of Trypanosoma brucei RNA-editing terminal uridylyl transferase 2 inhibitors. Chemical Biology & Drug Design 84, 131–139.CrossRefGoogle ScholarPubMed
de Souza, ML, de Oliveira Rezende Junior, C, Ferreira, RS, Espinoza Chavez, RM, Ferreira, LLG, Slafer, BW, Magalhaes, LG, Krogh, R, Oliva, G, Cruz, FC, Dias, LC and Andricopulo, AD (2019) Discovery of potent, reversible, and competitive cruzain inhibitors with trypanocidal activity: a structure-based drug design approach. Journal of Chemical Information and Modeling 62, 1028–1041.Google Scholar
Dietrich, RC, Alberca, LN, Ruiz, MD, Palestro, PH, Carrillo, C, Talevi, A and Gavernet, L (2018) Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening. European Journal of Medicinal Chemistry 149, 22–29.CrossRefGoogle ScholarPubMed
di Luccio, E and Koehl, P (2012) The H-factor as a novel quality metric for homology modeling. Journal of Clinical Bioinformatics 2, 18.CrossRefGoogle ScholarPubMed
DiMasi, JA, Grabowski, HG and Hansen, RW (2016) Innovation in the pharmaceutical industry: new estimates of R&D costs. Journal of Health Economics 47, 20–33.CrossRefGoogle ScholarPubMed
Dixon, SL, Smondyrev, AM, Knoll, EH, Rao, SN, Shaw, DE and Friesner, RA (2006) PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results. Journal of Computer-Aided Molecular Design 20, 647–671.CrossRefGoogle ScholarPubMed
Dorlo, TP, Balasegaram, M, Beijnen, JH and de Vries, PJ (2012) Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. Journal of Antimicrobial Chemotherapy 67, 2576–2597.CrossRefGoogle ScholarPubMed
Drews, J (1998) Innovation deficit revisited: reflections on the productivity of pharmaceutical R&D. Drugs Discovery Today 3, 491–494.CrossRefGoogle Scholar
Dube, D, Sharma, S, Singh, TP and Kaur, P (2014) Pharmacophore mapping, In silico screening and molecular docking to identify selective Trypanosoma brucei pteridine reductase inhibitors. Molecular Informatics 33, 124–134.CrossRefGoogle ScholarPubMed
Duncan, SM, Jones, NG and Mottram, JC (2017) Recent advances in Leishmania reverse genetics: manipulating a manipulative parasite. Molecular and Biochemical Parasitology 216, 30–38.CrossRefGoogle ScholarPubMed
Durrant, JD, Hall, L, Swift, RV, Landon, M, Schnaufer, A and Amaro, RE (2010) Novel naphthalene-based inhibitors of Trypanosoma brucei RNA editing ligase 1. PLoS Neglected Tropical Diseases 4, e803.CrossRefGoogle ScholarPubMed
Ekins, S, Williams, AJ, Krasowski, MD and Freundlich, JS (2011) In silico repositioning of approved drugs for rare and neglected diseases. Drug Discovery Today 16, 298–310.CrossRefGoogle ScholarPubMed
El-Sayed, NM, Myler, PJ, Bartholomeu, DC, Nilsson, D, Aggarwal, G, Tran, AN, Ghedin, E, Worthey, EA, Delcher, AL, Blandin, G, Westenberger, SJ, Caler, E, Cerqueira, GC, Branche, C, Haas, B, Anupama, A, Arner, E, Aslund, L, Attipoe, P, Bontempi, E, Bringaud, F, Burton, P, Cadag, E, Campbell, DA, Carrington, M, Crabtree, J, Darban, H, da Silveira, JF, de Jong, P, Edwards, K, Englund, PT, Fazelina, G, Feldblyum, T, Ferella, M, Frasch, AC, Gull, K, Horn, D, Hou, L, Huang, Y, Kindlund, E, Klingbeil, M, Kluge, S, Koo, H, Lacerda, D, Levin, MJ, Lorenzi, H, Louie, T, Machado, CR, McCulloch, R, McKenna, A, Mizuno, Y, Mottram, JC, Nelson, S, Ochaya, S, Osoegawa, K, Pai, G, Parsons, M, Pentony, M, Pettersson, U, Pop, M, Ramirez, JL, Rinta, J, Robertson, L, Salzberg, SL, Sanchez, DO, Seyler, A, Sharma, R, Shetty, J, Simpson, AJ, Sisk, E, Tammi, MT, Tarleton, R, Teixeira, S, Van Aken, S, Vogt, C, Ward, PN, Wickstead, B, Wortman, J, White, O, Fraser, CM, Stuart, KD and Andersson, B (2005a) The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science (New York, N.Y.) 309, 409–415.CrossRefGoogle Scholar
El-Sayed, NM, Myler, PJ, Blandin, G, Berriman, M, Crabtree, J, Aggarwal, G, Caler, E, Renauld, H, Worthey, EA, Hertz-Fowler, C, Ghedin, E, Peacock, C, Bartholomeu, DC, Haas, BJ, Tran, AN, Wortman, JR, Alsmark, UC, Angiuoli, S, Anupama, A, Badger, J, Bringaud, F, Cadag, E, Carlton, JM, Cerqueira, GC, Creasy, T, Delcher, AL, Djikeng, A, Embley, TM, Hauser, C, Ivens, AC, Kummerfeld, SK, Pereira-Leal, JB, Nilsson, D, Peterson, J, Salzberg, SL, Shallom, J, Silva, JC, Sundaram, J, Westenberger, S, White, O, Melville, SE, Donelson, JE, Andersson, B, Stuart, KD and Hall, N (2005b) Comparative genomics of trypanosomatid parasitic protozoa. Science (New York, N.Y.) 309, 404–409.CrossRefGoogle Scholar
Eramian, D, Shen, MY, Devos, D, Melo, F, Sali, A and Marti-Renom, MA (2006) A composite score for predicting errors in protein structure models. Protein Science 15, 1653–1666.CrossRefGoogle ScholarPubMed
Ferreira, LG and Andricopulo, AD (2016) Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective. Drug Discovery Today 21, 1699–1710.CrossRefGoogle ScholarPubMed
Field, MC, Horn, D, Fairlamb, AH, Ferguson, MAJ, Gray, DW, Read, KD, De Rycker, M, Torrie, LS, Wyatt, PG, Wyllie, S and Gilbert, IH (2017) Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nature Reviews Microbiology 15, 447.CrossRefGoogle Scholar
Fiser, A (2010) Template-based protein structure modeling. Methods in Molecular Biology 673, 73–94.CrossRefGoogle ScholarPubMed
Forli, S, Huey, R, Pique, ME, Sanner, MF, Goodsell, DS and Olson, AJ (2016) Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nature Protocols 11, 905–919.CrossRefGoogle ScholarPubMed
Fradera, X and Babaoglu, K (2017) Overview of methods and strategies for conducting virtual small molecule screening. Current Protocols in Chemical Biology 9, 196–212.CrossRefGoogle ScholarPubMed
Francisco, AF, Jayawardhana, S, Lewis, MD, White, KL, Shackleford, DM, Chen, G, Saunders, J, Osuna-Cabello, M, Read, KD, Charman, SA, Chatelain, E and Kelly, JM (2016) Nitroheterocyclic drugs cure experimental Trypanosoma cruzi infections more effectively in the chronic stage than in the acute stage. Scientific Reports 6, 35351.CrossRefGoogle ScholarPubMed
Friesner, RA, Murphy, RB, Repasky, MP, Frye, LL, Greenwood, JR, Halgren, TA, Sanschagrin, PC and Mainz, DT (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of Medicinal Chemistry 49, 6177–6196.CrossRefGoogle Scholar
Friggeri, L, Hargrove, TY, Rachakonda, G, Blobaum, AL, Fisher, P, de Oliveira, GM, da Silva, CF, Soeiro, MNC, Nes, WD, Lindsley, CW, Villalta, F, Guengerich, FP and Lepesheva, GI (2018) Sterol 14alpha-demethylase structure-based optimization of drug candidates for human infections with the protozoan trypanosomatidae. Journal of Medicinal Chemistry 61, 10910–10921.CrossRefGoogle ScholarPubMed
Fueller, F, Jehle, B, Putzker, K, Lewis, JD and Krauth-Siegel, RL (2012) High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin. Journal of Biological Chemistry 287, 8792–8802.CrossRefGoogle ScholarPubMed
Gaillard, T (2018) Evaluation of AutoDock and AutoDock Vina on the CASF-2013 Benchmark. Journal of Chemical Information and Modeling 58, 1697–1706.CrossRefGoogle ScholarPubMed
Gangwar, S, Baig, MS, Shah, P, Biswas, S, Batra, S, Siddiqi, MI and Goyal, N (2012) Identification of novel inhibitors of dipeptidylcarboxypeptidase of Leishmania donovani via ligand-based virtual screening and biological evaluation. Chemical Biology & Drug Design 79, 149–156.CrossRefGoogle ScholarPubMed
Gasteiger, J (2015) Cheminformatics: computing target complexity. Nature Chemistry 7, 619–620.CrossRefGoogle ScholarPubMed
Gaulton, A, Hersey, A, Nowotka, M, Bento, AP, Chambers, J, Mendez, D, Mutowo, P, Atkinson, F, Bellis, LJ, Cibrian-Uhalte, E, Davies, M, Dedman, N, Karlsson, A, Magarinos, MP, Overington, JP, Papadatos, G, Smit, I and Leach, AR (2017) The ChEMBL database in 2017. Nucleic Acids Research 45, D945–D954.CrossRefGoogle ScholarPubMed
Gelb, MH, Van Voorhis, WC, Buckner, FS, Yokoyama, K, Eastman, R, Carpenter, EP, Panethymitaki, C, Brown, KA and Smith, DF (2003) Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics. Molecular and Biochemical Parasitology 126, 155–163.CrossRefGoogle ScholarPubMed
Ghemtio, L, Perez-Nueno, VI, Leroux, V, Asses, Y, Souchet, M, Mavridis, L, Maigret, B and Ritchie, DW (2012) Recent trends and applications in 3D virtual screening. Combinatorial Chemistry & High Throughput Screening 15, 749–769.CrossRefGoogle ScholarPubMed
Ghofrani, HA, Osterloh, IH and Grimminger, F (2006) Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nature Reviews. Drug Discovery 5, 689–702.CrossRefGoogle ScholarPubMed
Gilbert, IH (2013) Drug discovery for neglected diseases: molecular target-based and phenotypic approaches. Journal of Medicinal Chemistry 56, 7719–7726.CrossRefGoogle ScholarPubMed
Gilbert, IH (2014) Target-based drug discovery for human African trypanosomiasis: selection of molecular target and chemical matter. Parasitology 141, 28–36.CrossRefGoogle ScholarPubMed
Gimeno, A, Ojeda-Montes, MJ, Tomas-Hernandez, S, Cereto-Massague, A, Beltran-Debon, R, Mulero, M, Pujadas, G and Garcia-Vallve, S (2019) The light and dark sides of virtual screening: what Is there to know? International Journal of Molecular Sciences 20, E1375.CrossRefGoogle Scholar
Gonzalez-Chavez, Z, Olin-Sandoval, V, Rodiguez-Zavala, JS, Moreno-Sanchez, R and Saavedra, E (2015) Metabolic control analysis of the Trypanosoma cruzi peroxide detoxification pathway identifies tryparedoxin as a suitable drug target. Biochimica et Biophysica Acta 1850, 263–273.CrossRefGoogle ScholarPubMed
Graul, AI, Pina, P, Cruces, E and Stringer, M (2017) The year's new drugs & biologics 2016: part I. Drugs Today (Barc) 53, 27–74.Google ScholarPubMed
Graul, AI, Pina, P and Stringer, M (2018) The year's new drugs and biologics 2017: part I. Drugs Today (Barc) 54, 35–84.CrossRefGoogle ScholarPubMed
Graul, AI, Pina, P, Cruces, E and Stringer, M (2019) The year's new drugs and biologics 2018: part I. Drugs Today (Barc) 55, 35–87.CrossRefGoogle ScholarPubMed
Grosdidier, A, Zoete, V and Michielin, O (2011) Swissdock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Research 39, W270–W277.CrossRefGoogle ScholarPubMed
Gupta, SC, Sung, B, Prasad, S, Webb, LJ and Aggarwal, BB (2013) Cancer drug discovery by repurposing: teaching new tricks to old dogs. Trends in Pharmacological Sciences 34, 508–517.CrossRefGoogle ScholarPubMed
Haga, JH, Ichikawa, K and Date, S (2016) Virtual screening techniques and current computational infrastructures. Current Pharmaceutical Design 22, 3576–3584.CrossRefGoogle ScholarPubMed
Hall, BS, Bot, C and Wilkinson, SR (2011) Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. Journal of Biological Chemistry 286, 13088–13095.CrossRefGoogle ScholarPubMed
Harigua-Souiai, E, Abdelkrim, YZ, Bassoumi-Jamoussi, I, Zakraoui, O, Bouvier, G, Essafi-Benkhadir, K, Banroques, J, Desdouits, N, Munier-Lehmann, H, Barhoumi, M, Tanner, NK, Nilges, M, Blondel, A and Guizani, I (2018) Identification of novel leishmanicidal molecules by virtual and biochemical screenings targeting Leishmania eukaryotic translation initiation factor 4A. PLoS Neglected Tropical Diseases 12, e0006160.CrossRefGoogle ScholarPubMed
Herrera-Mayorga, V, Lara-Ramirez, EE, Chacon-Vargas, KF, Aguirre-Alvarado, C, Rodriguez-Paez, L, Alcantara-Farfan, V, Cordero-Martinez, J, Nogueda-Torres, B, Reyes-Espinosa, F, Bocanegra-Garcia, V and Rivera, G (2019) Structure-based virtual screening and in vitro evaluation of new Trypanosoma cruzi cruzain inhibitors. International Journal of Molecular Sciences 20, E1742.CrossRefGoogle ScholarPubMed
Herrmann, FC, Lenz, M, Jose, J, Kaiser, M, Brun, R and Schmidt, TJ (2015) In silico identification and in vitro activity of novel natural inhibitors of Trypanosoma brucei glyceraldehyde-3-phosphate-dehydrogenase. Molecules 20, 16154–16169.CrossRefGoogle ScholarPubMed
Hollingsworth, TD (2018) Counting down the 2020 goals for 9 neglected tropical diseases: what have We learned from quantitative analysis and transmission modeling? Clinical Infectious Diseases 66, S237–S244.CrossRefGoogle ScholarPubMed
Hornberg, JJ, Bruggeman, FJ, Bakker, BM and Westerhoff, HV (2007) Metabolic control analysis to identify optimal drug targets. Progress in Drug Research 64, 173–189.Google ScholarPubMed
Hu, B and Lill, MA (2014) Pharmdock: a pharmacophore-based docking program. Journal of Cheminformatics 6, 14.CrossRefGoogle ScholarPubMed
Hughes, JP, Rees, S, Kalindjian, SB and Philpott, KL (2011) Principles of early drug discovery. British Journal of Pharmacology 162, 1239–1249.CrossRefGoogle ScholarPubMed
Humphrey, W, Dalke, A and Schulten, K (1996) VMD: visual molecular dynamics. Journal of Molecular Graphics 14, 33–38, 27–38.CrossRefGoogle ScholarPubMed
Hutton, JA, Goncalves, V, Brannigan, JA, Paape, D, Wright, MH, Waugh, TM, Roberts, SM, Bell, AS, Wilkinson, AJ, Smith, DF, Leatherbarrow, RJ and Tate, EW (2014) Structure-based design of potent and selective Leishmania N-myristoyltransferase inhibitors. Journal of Medicinal Chemistry 57, 8664–8670.CrossRefGoogle ScholarPubMed
Jain, AN (2009) Effects of protein conformation in docking: improved pose prediction through protein pocket adaptation. Journal of Computer-Aided Molecular Design 23, 355–374.CrossRefGoogle ScholarPubMed
Jain, K and Jain, NK (2013) Novel therapeutic strategies for treatment of visceral leishmaniasis. Drug Discovery Today 18, 1272–1281.CrossRefGoogle ScholarPubMed
James Abraham, TM, Schulz, R, Pall, S, Smith, J, Hess, B and Lindahl, E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1, 19–25.CrossRefGoogle Scholar
Jhingran, A, Chawla, B, Saxena, S, Barrett, MP and Madhubala, R (2009) Paromomycin: uptake and resistance in Leishmania donovani. Molecular and Biochemical Parasitology 164, 111–117.CrossRefGoogle ScholarPubMed
Johnson, MA, Maggiora, GM and Meeting, ACS (1990) Concepts and Applications of Molecular Similarity. New York City, USA: Wiley.Google Scholar
Jones, G, Willett, P, Glen, RC, Leach, AR and Taylor, R (1997) Development and validation of a genetic algorithm for flexible docking. Journal of Molecular Biology 267, 727–748.CrossRefGoogle ScholarPubMed
Jones, NG, Catta-Preta, CMC, Lima, A and Mottram, JC (2018) Genetically validated drug targets in Leishmania: current knowledge and future prospects. ACS Infectious Diseases 4, 467–477.CrossRefGoogle ScholarPubMed
Kansiime, F, Adibaku, S, Wamboga, C, Idi, F, Kato, CD, Yamuah, L, Vaillant, M, Kioy, D, Olliaro, P and Matovu, E (2018) A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda. Parasites and Vectors 11, 1–11.CrossRefGoogle ScholarPubMed
Kashif, M, Hira, SK, Upadhyaya, A, Gupta, U, Singh, R, Paladhi, A, Khan, FI, Rub, A and Manna, PP (2019) In silico studies and evaluation of antiparasitic role of a novel pyruvate phosphate dikinase inhibitor in Leishmania donovani infected macrophages. International Journal of Antimicrobial Agents 53, 508–514.CrossRefGoogle ScholarPubMed
Kawasaki, Y and Freire, E (2011) Finding a better path to drug selectivity. Drug Discovery Today 16, 985–990.CrossRefGoogle ScholarPubMed
Kelley, BP, Brown, SP, Warren, GL and Muchmore, SW (2015) POSIT: flexible shape-guided docking for pose prediction. Journal of Chemical Information and Modeling 55, 1771–1780.CrossRefGoogle ScholarPubMed
Khare, P, Gupta, AK, Gajula, PK, Sunkari, KY, Jaiswal, AK, Das, S, Bajpai, P, Chakraborty, TK, Dube, A and Saxena, AK (2012) Identification of novel S-adenosyl-L-homocysteine hydrolase inhibitors through homology-model-based virtual screening, synthesis, and biological evaluation. Journal of Chemical Information and Modeling 52, 777–791.CrossRefGoogle Scholar
Khare, S, Roach, SL, Barnes, SW, Hoepfner, D, Walker, JR, Chatterjee, AK, Neitz, RJ, Arkin, MR, McNamara, CW, Ballard, J, Lai, Y, Fu, Y, Molteni, V, Yeh, V, McKerrow, JH, Glynne, RJ and Supek, F (2015) Utilizing chemical genomics to identify cytochrome b as a novel drug target for Chagas disease. PLoS Pathogens 11, e1005058.CrossRefGoogle ScholarPubMed
Khare, S, Nagle, AS, Biggart, A, Lai, YH, Liang, F, Davis, LC, Barnes, SW, Mathison, CJN, Myburgh, E, Gao, M-y, Gillespie, JR, Liu, X, Tan, JL, Stinson, M, Rivera, IC, Ballard, J, Yeh, V, Groessl, T, Federe, G, Koh, HXY, Venable, JD, Bursulaya, B, Shapiro, M, Mishra, PK, Spraggon, G, Brock, A, Mottram, JC and Buckner, FS (2016) Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature 537, 229–233.CrossRefGoogle ScholarPubMed
Kim, S, Chen, J, Cheng, T, Gindulyte, A, He, J, He, S, Li, Q, Shoemaker, BA, Thiessen, PA, Yu, B, Zaslavsky, L, Zhang, J and Bolton, EE (2019) Pubchem 2019 update: improved access to chemical data. Nucleic Acids Research 47, D1102–D1109.CrossRefGoogle ScholarPubMed
King-Keller, S, Li, M, Smith, A, Zheng, S, Kaur, G, Yang, X, Wang, B and Docampo, R (2010) Chemical validation of phosphodiesterase C as a chemotherapeutic target in Trypanosoma cruzi, the etiological agent of Chagas’ disease. Antimicrobial Agents and Chemotherapy 54, 3738–3745.CrossRefGoogle Scholar
Konkle, ME, Hargrove, TY, Kleshchenko, YY, von Kries, JP, Ridenour, W, Uddin, MJ, Caprioli, RM, Marnett, LJ, Nes, WD, Villalta, F, Waterman, MR and Lepesheva, GI (2009) Indomethacin amides as a novel molecular scaffold for targeting Trypanosoma cruzi sterol 14alpha-demethylase. Journal of Medicinal Chemistry 52, 2846–2853.CrossRefGoogle ScholarPubMed
Kontoyianni, M (2017) Docking and virtual screening in drug discovery. Methods in Molecular Biology 1647, 255–266.CrossRefGoogle ScholarPubMed
Kraus, JM, Tatipaka, HB, McGuffin, SA, Chennamaneni, NK, Karimi, M, Arif, J, Verlinde, CL, Buckner, FS and Gelb, MH (2010) Second generation analogues of the cancer drug clinical candidate tipifarnib for anti-Chagas disease drug discovery. Journal of Medicinal Chemistry 53, 3887–3898.CrossRefGoogle ScholarPubMed
Krauth-Siegel, RL, Enders, B, Henderson, GB, Fairlamb, AH and Schirmer, RH (1987) Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. European Journal of Biochemistry 164, 123–128.CrossRefGoogle ScholarPubMed
Lamotte, S, Aulner, N, Spath, GF and Prina, E (2019) Discovery of novel hit compounds with broad activity against visceral and cutaneous Leishmania species by comparative phenotypic screening. Scientific Reports 9, 438.CrossRefGoogle ScholarPubMed
Lander, N, Chiurillo, MA and Docampo, R (2016) Genome editing by CRISPR/Cas9: a game change in the genetic manipulation of protists. Journal of Eukaryotic Microbiology 63, 679–690.CrossRefGoogle ScholarPubMed
Lara-Ramirez, EE, Lopez-Cedillo, JC, Nogueda-Torres, B, Kashif, M, Garcia-Perez, C, Bocanegra-Garcia, V, Agusti, R, Uhrig, ML and Rivera, G (2017) An in vitro and in vivo evaluation of new potential trans-sialidase inhibitors of Trypanosoma cruzi predicted by a computational drug repositioning method. European Journal of Medicinal Chemistry 132, 249–261.CrossRefGoogle Scholar
Lepesheva, GI, Ott, RD, Hargrove, TY, Kleshchenko, YY, Schuster, I, Nes, WD, Hill, GC, Villalta, F and Waterman, MR (2007) Sterol 14alpha-demethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth. Chemistry & Biology 14, 1283–1293.CrossRefGoogle ScholarPubMed
Leroux, AE and Krauth-Siegel, RL (2016) Thiol redox biology of trypanosomatids and potential targets for chemotherapy. Molecular and Biochemical Parasitology 206, 67–74.CrossRefGoogle ScholarPubMed
Lesnik, S, Stular, T, Brus, B, Knez, D, Gobec, S, Janezic, D and Konc, J (2015) LiSiCA: a software for ligand-based virtual screening and its application for the discovery of butyrylcholinesterase inhibitors. Journal of Chemical Information and Modeling 55, 1521–1528.CrossRefGoogle ScholarPubMed
Li, AP (2001) Screening for human ADME/Tox drug properties in drug discovery. Drug Discovery Today 6, 357–366.CrossRefGoogle ScholarPubMed
Lipinski, CA, Lombardo, F, Dominy, BW and Feeney, PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 46, 3–26.CrossRefGoogle ScholarPubMed
Llanos, MA, Sbaraglini, ML, Villalba, ML, Ruiz, MD, Carrillo, C, Alba Soto, C, Talevi, A, Angeli, A, Parkkila, S, Supuran, CT and Gavernet, L (2020) A structure-based approach towards the identification of novel antichagasic compounds: Trypanosoma cruzi carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry 35, 21–30.CrossRefGoogle ScholarPubMed
Lo, YC, Rensi, SE, Torng, W and Altman, RB (2018) Machine learning in chemoinformatics and drug discovery. Drug Discovery Today 23, 1538–1546.CrossRefGoogle ScholarPubMed
Lu, J, Vodnala, SK, Gustavsson, AL, Gustafsson, TN, Sjoberg, B, Johansson, HA, Kumar, S, Tjernberg, A, Engman, L, Rottenberg, ME and Holmgren, A (2013) Ebsulfur is a benzisothiazolone cytocidal inhibitor targeting the trypanothione reductase of Trypanosoma brucei. Journal of Biological Chemistry 288, 27456–27468.CrossRefGoogle ScholarPubMed
Luo, Y, Li, BZ, Liu, D, Zhang, L, Chen, Y, Jia, B, Zeng, BX, Zhao, H and Yuan, YJ (2015) Engineered biosynthesis of natural products in heterologous hosts. Chemical Society Reviews 44, 5265–5290.CrossRefGoogle ScholarPubMed
Ma, XH, Jia, J, Zhu, F, Xue, Y, Li, ZR and Chen, YZ (2009) Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries. Combinatorial Chemistry & High Throughput Screening 12, 344–357.CrossRefGoogle ScholarPubMed
Magarinos, MP, Carmona, SJ, Crowther, GJ, Ralph, SA, Roos, DS, Shanmugam, D, Van Voorhis, WC and Aguero, F (2012) TDR Targets: a chemogenomics resource for neglected diseases. Nucleic Acids Research 40, D1118–D1127.CrossRefGoogle ScholarPubMed
Maluf, FV, Andricopulo, AD, Oliva, G and Guido, RV (2013) A pharmacophore-based virtual screening approach for the discovery of Trypanosoma cruzi GAPDH inhibitors. Future Medicinal Chemistry 5, 2019–2035.CrossRefGoogle ScholarPubMed
Mansuri, R, Kumar, A, Rana, S, Panthi, B, Ansari, MY, Das, S, Dikhit, MR, Sahoo, GC and Das, P (2017) In vitro evaluation of antileishmanial activity of computationally screened compounds against ascorbate peroxidase to combat amphotericin B drug resistance. Antimicrobial Agents and Chemotherapy 61, e02429-16.CrossRefGoogle ScholarPubMed
Marchese, L, Nascimento, JF, Damasceno, FS, Bringaud, F, Michels, PAM and Silber, AM (2018) The uptake and metabolism of amino acids, and their unique role in the biology of pathogenic trypanosomatids. Pathogens (Basel, Switzerland) 7, E36.Google ScholarPubMed
Mavridis, L, Hudson, BD and Ritchie, DW (2007) Toward high throughput 3D virtual screening using spherical harmonic surface representations. Journal of Chemical Information and Modeling 47, 1787–1796.CrossRefGoogle ScholarPubMed
Maxfield, L and Crane, JS (2019) Leishmaniasis. In StatPearls. Florida, USA: StatPearls Publishing, pp. 1–9.Google ScholarPubMed
Meiering, S, Inhoff, O, Mies, J, Vincek, A, Garcia, G, Kramer, B, Dormeyer, M and Krauth-Siegel, RL (2005) Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis. Journal of Medicinal Chemistry 48, 4793–4802.CrossRefGoogle ScholarPubMed
Menna-Barreto, RFS (2019) Cell death pathways in pathogenic trypanosomatids: lessons of (over)kill. Cell death & disease 10, 93.CrossRefGoogle ScholarPubMed
Menzies, SK, Tulloch, LB, Florence, GJ and Smith, TK (2018) The trypanosome alternative oxidase: a potential drug target? Parasitology 145, 175–183.CrossRefGoogle ScholarPubMed
Mesu, V, Kalonji, WM, Bardonneau, C, Mordt, OV, Blesson, S, Simon, F, Delhomme, S, Bernhard, S, Kuziena, W, Lubaki, JF, Vuvu, SL, Ngima, PN, Mbembo, HM, Ilunga, M, Bonama, AK, Heradi, JA, Solomo, JLL, Mandula, G, Badibabi, LK, Dama, FR, Lukula, PK, Tete, DN, Lumbala, C, Scherrer, B, Strub-Wourgaft, N and Tarral, A (2018) Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet (London, England) 391, 144–154.CrossRefGoogle ScholarPubMed
Meyerhoff, A (1999) U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clinical infectious Diseases 28, 42–48, discussion 49–51.CrossRefGoogle Scholar
Meyskens, FL, Kingsley, EM, Glattke, T, Loescher, L and Booth, A (1986) A phase II study of alpha-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma. Investigational New Drugs 4, 257–262.CrossRefGoogle ScholarPubMed
Mishra, AK, Singh, N, Agnihotri, P, Mishra, S, Singh, SP, Kolli, BK, Chang, KP, Sahasrabuddhe, AA, Siddiqi, MI and Pratap, JV (2017) Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization. Journal of Computer-Aided Molecular Design 31, 547–562.CrossRefGoogle ScholarPubMed
Mogk, S, Bosselmann, CM, Mudogo, CN, Stein, J, Wolburg, H and Duszenko, M (2017) African trypanosomes and brain infection – the unsolved question. Biological Reviews of the Cambridge Philosophical Society 92, 1675–1687.CrossRefGoogle ScholarPubMed
Morillo, CA, Waskin, H, Sosa-Estani, S, Del Carmen Bangher, M, Cuneo, C, Milesi, R, Mallagray, M, Apt, W, Beloscar, J, Gascon, J, Molina, I, Echeverria, LE, Colombo, H, Perez-Molina, JA, Wyss, F, Meeks, B, Bonilla, LR, Gao, P, Wei, B, McCarthy, M and Yusuf, S (2017) Benznidazole and posaconazole in eliminating parasites in asymptomatic T. Cruzi carriers: the STOP-CHAGAS trial. Journal of the American College of Cardiology 69, 939–947.CrossRefGoogle ScholarPubMed
Morris, GM, Huey, R, Lindstrom, W, Sanner, MF, Belew, RK, Goodsell, DS and Olson, AJ (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility. Journal of Computational Chemistry 30, 2785–2791.CrossRefGoogle ScholarPubMed
Mpamhanga, CP, Spinks, D, Tulloch, LB, Shanks, EJ, Robinson, DA, Collie, IT, Fairlamb, AH, Wyatt, PG, Frearson, JA, Hunter, WN, Gilbert, IH and Brenk, R (2009) One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening. Journal of Medicinal Chemistry 52, 4454–4465.CrossRefGoogle ScholarPubMed
Mukhopadhyay, R and Madhubala, R (1994) Effect of antioxidants on the growth and polyamine levels of Leishmania donovani. Biochemical Pharmacology 47, 611–615.CrossRefGoogle ScholarPubMed
Novac, N (2013) Challenges and opportunities of drug repositioning. Trends in Pharmacological Sciences 34, 267–272.CrossRefGoogle ScholarPubMed
Novick, PA, Ortiz, OF, Poelman, J, Abdulhay, AY and Pande, VS (2013) SWEETLEAD: an in silico database of approved drugs, regulated chemicals, and herbal isolates for computer-aided drug discovery. PLoS ONE 8, e79568.CrossRefGoogle Scholar
Nowicki, MW, Tulloch, LB, Worralll, L, McNae, IW, Hannaert, V, Michels, PA, Fothergill-Gilmore, LA, Walkinshaw, MD and Turner, NJ (2008) Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis. Bioorganic & Medicinal Chemistry 16, 5050–5061.CrossRefGoogle ScholarPubMed
Nwaka, S, Ramirez, B, Brun, R, Maes, L, Douglas, F and Ridley, R (2009) Advancing drug innovation for neglected diseases – criteria for lead progression. PLoS Neglected Tropical Diseases 3, e440.CrossRefGoogle ScholarPubMed
Ochoa, R, Watowich, SJ, Florez, A, Mesa, CV, Robledo, SM and Muskus, C (2016) Drug search for leishmaniasis: a virtual screening approach by grid computing. Journal of Computer-Aided Molecular Design 30, 541–552.CrossRefGoogle ScholarPubMed
Ochoa, R, Rocha-Roa, C, Marin-Villa, M, Robledo, SM and Varela, MR (2018) Search of allosteric inhibitors and associated proteins of an AKT-like kinase from Trypanosoma cruzi. International Journal of Molecular Sciences 19, E3951.CrossRefGoogle ScholarPubMed
Ochoa, R, Garcia, E, Robledo, SM and Cardona, GW (2019) Virtual and experimental screening of phenylfuranchalcones as potential anti-Leishmania candidates. Journal of Molecular Graphics & Modelling 91, 164–171.CrossRefGoogle ScholarPubMed
Olin-Sandoval, V, Gonzalez-Chavez, Z, Berzunza-Cruz, M, Martinez, I, Jasso-Chavez, R, Becker, I, Espinoza, B, Moreno-Sanchez, R and Saavedra, E (2012) Drug target validation of the trypanothione pathway enzymes through metabolic modelling. FEBS Journal 279, 1811–1833.CrossRefGoogle ScholarPubMed
Oprea, TI (2002) Virtual screening in lead discovery: a viewpoint. Molecules 7, 51–62.CrossRefGoogle Scholar
Orban, OC, Korn, RS, Benitez, D, Medeiros, A, Preu, L, Loaec, N, Meijer, L, Koch, O, Comini, MA and Kunick, C (2016) 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms. Bioorganic & Medicinal Chemistry 24, 3790–3800.CrossRefGoogle ScholarPubMed
Ortega, V, Giorgio, S and de Paula, E (2017) Liposomal formulations in the pharmacological treatment of leishmaniasis: a review. Journal of Liposome Research 27, 234–248.CrossRefGoogle ScholarPubMed
Osorio-Mendez, JF and Cevallos, AM (2018) Discovery and genetic validation of chemotherapeutic targets for Chagas’ disease. Frontiers in cellular and infection microbiology 8, 439.CrossRefGoogle ScholarPubMed
Palos, I, Lara-Ramirez, EE, Lopez-Cedillo, JC, Garcia-Perez, C, Kashif, M, Bocanegra-Garcia, V, Nogueda-Torres, B and Rivera, G (2017) Repositioning FDA drugs as potential cruzain inhibitors from Trypanosoma cruzi: virtual screening, in vitro and in vivo studies. Molecules 22, E1015.CrossRefGoogle Scholar
Parameswaran, S, Saudagar, P, Dubey, VK and Patra, S (2014) Discovery of novel anti-leishmanial agents targeting LdLip3 lipase. Journal of Molecular Graphics & Modelling 49, 68–79.CrossRefGoogle ScholarPubMed
Perez-Molina, JA and Molina, I (2018) Chagas disease. Lancet (London, England) 391, 82–94.CrossRefGoogle ScholarPubMed
Pieper, U, Webb, BM, Dong, GQ, Schneidman-Duhovny, D, Fan, H, Kim, SJ, Khuri, N, Spill, YG, Weinkam, P, Hammel, M, Tainer, JA, Nilges, M and Sali, A (2014) Modbase, a database of annotated comparative protein structure models and associated resources. Nucleic Acids Research 42, D336–D346.CrossRefGoogle ScholarPubMed
Pierce, BG, Hourai, Y and Weng, Z (2011) Accelerating protein docking in ZDOCK using an advanced 3D convolution library. PLoS ONE 6, e24657.CrossRefGoogle ScholarPubMed
Pinto-Martinez, AK, Rodriguez-Duran, J, Serrano-Martin, X, Hernandez-Rodriguez, V and Benaim, G (2018) Mechanism of action of miltefosine on Leishmania donovani involves the impairment of acidocalcisome function and the activation of the sphingosine-dependent plasma membrane Ca(2+) channel. Antimicrobial Agents and Chemotherapy 62, e01614-17.CrossRefGoogle ScholarPubMed
Pollastri, MP and Campbell, RK (2011) Target repurposing for neglected diseases. Future Medicinal Chemistry 3, 1307–1315.CrossRefGoogle ScholarPubMed
Ponte-Sucre, A, Gamarro, F, Dujardin, JC, Barrett, MP, Lopez-Velez, R, Garcia-Hernandez, R, Pountain, AW, Mwenechanya, R and Papadopoulou, B (2017) Drug resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Neglected Tropical Diseases 11, e0006052.CrossRefGoogle ScholarPubMed
Prieto, JJ, Talevi, A and Bruno-Blanch, LE (2006) Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition. Molecular Diversity 10, 361–375.CrossRefGoogle ScholarPubMed
Priotto, G, Kasparian, S, Mutombo, W, Ngouama, D, Ghorashian, S, Arnold, U, Ghabri, S, Baudin, E, Buard, V, Kazadi-Kyanza, S, Ilunga, M, Mutangala, W, Pohlig, G, Schmid, C, Karunakara, U, Torreele, E and Kande, V (2009) Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet (London, England) 374, 56–64.CrossRefGoogle ScholarPubMed
Prokopczyk, IM, Ribeiro, JF, Sartori, GR, Sesti-Costa, R, Silva, JS, Freitas, RF, Leitao, A and Montanari, CA (2014) Integration of methods in cheminformatics and biocalorimetry for the design of trypanosomatid enzyme inhibitors. Future Medicinal Chemistry 6, 17–33.CrossRefGoogle ScholarPubMed
Raether, W and Seidenath, H (1983) The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica. Annals of Tropical Medicine & Parasitology 77, 13–26.CrossRefGoogle ScholarPubMed
Rarey, M, Kramer, B, Lengauer, T and Klebe, G (1996) A fast flexible docking method using an incremental construction algorithm. Journal of Molecular Biology 261, 470–489.CrossRefGoogle ScholarPubMed
Rashmi, M and Swati, D (2015) In silico drug re-purposing against African sleeping sickness using GlcNAc-PI de-N-acetylase as an experimental target. Computational Biology and Chemistry 59, 87–94.CrossRefGoogle ScholarPubMed
Rassi, A Jr, Rassi, A and Marin-Neto, JA (2010) Chagas disease. Lancet (London, England), 375, 1388–1402.CrossRefGoogle ScholarPubMed
Reigada, C, Valera-Vera, EA, Saye, M, Errasti, AE, Avila, CC, Miranda, MR and Pereira, CA (2017) Trypanocidal effect of isotretinoin through the inhibition of polyamine and amino acid transporters in Trypanosoma cruzi. PLoS Neglected Tropical Diseases 11, e0005472.CrossRefGoogle ScholarPubMed
Reigada, C, Phanstiel, Ot, Miranda, MR and Pereira, CA (2018) Targeting polyamine transport in Trypanosoma cruzi. European Journal of Medicinal Chemistry 147, 1–6.CrossRefGoogle ScholarPubMed
Reigada, C, Saye, M, Phanstiel, Ot, Valera-Vera, E, Miranda, MR and Pereira, CA (2019) Identification of Trypanosoma cruzi polyamine transport inhibitors by computational drug repurposing. Frontiers in Medicine (Lausanne) 6, 256.CrossRefGoogle ScholarPubMed
Rester, U (2008) From virtuality to reality – virtual screening in lead discovery and lead optimization: a medicinal chemistry perspective. Current Opinion in Drug Discovery & Development 11, 559–568.Google ScholarPubMed
Roberts, CW, McLeod, R, Rice, DW, Ginger, M, Chance, ML and Goad, LJ (2003) Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa. Molecular and Biochemical Parasitology 126, 129–142.CrossRefGoogle ScholarPubMed
Rodriguez, D, Chakraborty, S, Warnick, E, Crane, S, Gao, ZG, O'Connor, R, Jacobson, KA and Carlsson, J (2016) Structure-based screening of uncharted chemical space for atypical adenosine receptor agonists. ACS Chemical Biology 11, 2763–2772.CrossRefGoogle ScholarPubMed
Rogers, KE, Keranen, H, Durrant, JD, Ratnam, J, Doak, A, Arkin, MR and McCammon, JA (2012) Novel cruzain inhibitors for the treatment of Chagas’ disease. Chemical Biology & Drug Design 80, 398–405.CrossRefGoogle ScholarPubMed
Ruda, GF, Campbell, G, Alibu, VP, Barrett, MP, Brenk, R and Gilbert, IH (2010) Virtual fragment screening for novel inhibitors of 6-phosphogluconate dehydrogenase. Bioorganic & Medicinal Chemistry 18, 5056–5062.CrossRefGoogle ScholarPubMed
Sardana, D, Zhu, C, Zhang, M, Gudivada, RC, Yang, L and Jegga, AG (2011) Drug repositioning for orphan diseases. Briefings in Bioinformatics 12, 346–356.CrossRefGoogle ScholarPubMed
Saye, M, Gauna, L, Valera-Vera, E, Reigada, C, Miranda, MR and Pereira, CA (2020) Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069. PLoS Neglected Tropical Diseases 14, e0007481.CrossRefGoogle ScholarPubMed
Schierz, AC (2009) Virtual screening of bioassay data. Journal of Cheminformatics 1, 21.CrossRefGoogle ScholarPubMed
Schmidtke, P, Le Guilloux, V, Maupetit, J and Tuffery, P (2010) fpocket: online tools for protein ensemble pocket detection and tracking. Nucleic Acids Research 38, W582–W589.CrossRefGoogle ScholarPubMed
Schneider, G (2010) Virtual screening: an endless staircase? Nature Reviews. Drug Discovery 9, 273–276.CrossRefGoogle ScholarPubMed
Scior, T, Bender, A, Tresadern, G, Medina-Franco, JL, Martinez-Mayorga, K, Langer, T, Cuanalo-Contreras, K and Agrafiotis, DK (2012) Recognizing pitfalls in virtual screening: a critical review. Journal of Chemical Information and Modeling 52, 867–881.CrossRefGoogle ScholarPubMed
Sharlow, E, Golden, JE, Dodson, H, Morris, M, Hesser, M, Lyda, T, Leimgruber, S, Schroeder, CE, Flaherty, DP, Weiner, WS, Simpson, D, Lazo, JS, Aube, J and Morris, JC (2010a) Identification of Inhibitors of Trypanosoma brucei Hexokinases. In Probe Reports from the NIH Molecular Libraries Program. Bethesda, USA: National Center for Biotechnology Information, pp. 1–44.Google Scholar
Sharlow, ER, Lyda, TA, Dodson, HC, Mustata, G, Morris, MT, Leimgruber, SS, Lee, KH, Kashiwada, Y, Close, D, Lazo, JS and Morris, JC (2010b) A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. PLoS Neglected Tropical Diseases 4, e659.CrossRefGoogle Scholar
Shen, MY and Sali, A (2006) Statistical potential for assessment and prediction of protein structures. Protein Science 15, 2507–2524.CrossRefGoogle ScholarPubMed
Sindermann, H, Croft, SL, Engel, KR, Bommer, W, Eibl, HJ, Unger, C and Engel, J (2004) Miltefosine (Impavido): the first oral treatment against leishmaniasis. Medical Microbiology and Immunology 193, 173–180.CrossRefGoogle ScholarPubMed
Singh, J, Srivastava, A, Jha, P, Sinha, KK and Kundu, B (2015) L-Asparaginase as a new molecular target against leishmaniasis: insights into the mechanism of action and structure-based inhibitor design. Molecular BioSystems 11, 1887–1896.CrossRefGoogle ScholarPubMed
Singhal, S, Mehta, J, Desikan, R, Ayers, D, Roberson, P, Eddlemon, P, Munshi, N, Anaissie, E, Wilson, C, Dhodapkar, M, Zeddis, J and Barlogie, B (1999) Antitumor activity of thalidomide in refractory multiple myeloma. New England Journal of Medicine 341, 1565–1571.CrossRefGoogle ScholarPubMed
Smithson, DC, Lee, J, Shelat, AA, Phillips, MA and Guy, RK (2010) Discovery of potent and selective inhibitors of Trypanosoma brucei ornithine decarboxylase. Journal of Biological Chemistry 285, 16771–16781.CrossRefGoogle ScholarPubMed
Soares, MB, Silva, CV, Bastos, TM, Guimaraes, ET, Figueira, CP, Smirlis, D and Azevedo, WF Jr (2012). Anti-Trypanosoma cruzi activity of nicotinamide. Acta Tropica, 122, 224–229.CrossRefGoogle ScholarPubMed
Soares Medeiros, LC, South, L, Peng, D, Bustamante, JM, Wang, W, Bunkofske, M, Perumal, N, Sanchez-Valdez, F and Tarleton, RL (2017) Rapid, selection-free, high-efficiency genome editing in protozoan parasites using CRISPR-Cas9 ribonucleoproteins. MBio 8, e01788-17.CrossRefGoogle ScholarPubMed
Sosa, EJ, Burguener, G, Lanzarotti, E, Defelipe, L, Radusky, L, Pardo, AM, Marti, M, Turjanski, AG and Fernandez Do Porto, D (2018) Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens. Nucleic Acids Research 46, D413–D418.CrossRefGoogle ScholarPubMed
Sousa, SF, Ribeiro, AJ, Coimbra, JT, Neves, RP, Martins, SA, Moorthy, NS, Fernandes, PA and Ramos, MJ (2013) Protein-ligand docking in the new millennium--a retrospective of 10 years in the field. Current Medicinal Chemistry 20, 2296–2314.CrossRefGoogle Scholar
Spinks, D, Ong, HB, Mpamhanga, CP, Shanks, EJ, Robinson, DA, Collie, IT, Read, KD, Frearson, JA, Wyatt, PG, Brenk, R, Fairlamb, AH and Gilbert, IH (2011) Design, synthesis and biological evaluation of novel inhibitors of Trypanosoma brucei pteridine reductase 1. ChemMedChem 6, 302–308.CrossRefGoogle ScholarPubMed
Sterling, T and Irwin, JJ (2015) ZINC 15 – ligand discovery for everyone. Journal of Chemical Information and Modeling 55, 2324–2337.CrossRefGoogle ScholarPubMed
Stevanovic, S, Perdih, A, Sencanski, M, Glisic, S, Duarte, M, Tomas, AM, Sena, FV, Sousa, FM, Pereira, MM and Solmajer, T (2018) In silico discovery of a substituted 6-methoxy-quinalidine with leishmanicidal activity in Leishmania infantum. Molecules 23, E772.CrossRefGoogle ScholarPubMed
Stevanovic, S, Sencanski, M, Danel, M, Menendez, C, Belguedj, R, Bouraiou, A, Nikolic, K, Cojean, S, Loiseau, PM, Glisic, S, Baltas, M and Garcia-Sosa, AT (2019) Synthesis, In silico, and In vitro evaluation of anti-leishmanial activity of oxadiazoles and indolizine containing compounds flagged against anti-targets. Molecules 24, E1282.CrossRefGoogle ScholarPubMed
Steverding, D (2008) The history of African trypanosomiasis. Parasites & Vectors 1, 3.CrossRefGoogle ScholarPubMed
Stouch, TR, Kenyon, JR, Johnson, SR, Chen, XQ, Doweyko, A and Li, Y (2003) In silico ADME/Tox: why models fail. Journal of Computer-Aided Molecular Design 17, 83–92.CrossRefGoogle ScholarPubMed
Stumpfe, D and Bajorath, J (2012) Exploring activity cliffs in medicinal chemistry. Journal of Medicinal Chemistry 55, 2932–2942.CrossRefGoogle ScholarPubMed
Sun, W, Sanderson, PE and Zheng, W (2016) Drug combination therapy increases successful drug repositioning. Drug Discovery Today 21, 1189–1195.CrossRefGoogle ScholarPubMed
Talevi, A, Gavernet, L and Bruno-Blanch, LE (2009) Combined virtual screening strategies. Current Computer-Aided Drug Design 5, 23–37.CrossRefGoogle Scholar
Tiwari, N, Tanwar, N and Munde, M (2018) Molecular insights into trypanothione reductase-inhibitor interaction: a structure-based review. Arch Pharm (Weinheim) 351, e1700373.CrossRefGoogle ScholarPubMed
Todeschini, R, Consonni, V and Gramatica, P (2009) Chemometrics in QSAR. In Brown, S, Walczak, B and Tauler, R (eds), Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, Vol. 4. Amsterdam, Netherlands: Elsevier, pp. 129–172.Google Scholar
Torrie, LS, Wyllie, S, Spinks, D, Oza, SL, Thompson, S, Harrison, JR, Gilbert, IH, Wyatt, PG, Fairlamb, AH and Frearson, JA (2009) Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis. Journal of Biological Chemistry 284, 36137–36145.CrossRefGoogle ScholarPubMed
Tropsha, A (2010) Best practices for QSAR model development, validation, and exploitation. Molecular Informatics 29, 476–488.CrossRefGoogle ScholarPubMed
Trott, O and Olson, AJ (2010) Autodock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry 31, 455–461.Google ScholarPubMed
Uran Landaburu, L, Berenstein, AJ, Videla, S, Maru, P, Shanmugam, D, Chernomoretz, A and Aguero, F. (2019) TDR Targets 6: driving drug discovery for human pathogens through intensive chemogenomic data integration. Nucleic Acids Research 48, gkz999. doi: 10.1093/nar/gkz999 5611677CrossRefGoogle Scholar
Urbina, JA (2015) Recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives. Journal of Eukaryotic Microbiology 62, 149–156.CrossRefGoogle Scholar
Vainio, MJ, Puranen, JS and Johnson, MS (2009) ShaEP: molecular overlay based on shape and electrostatic potential. Journal of Chemical Information and Modeling 49, 492–502.CrossRefGoogle ScholarPubMed
Valera-Vera, EA, Saye, M, Reigada, C, Miranda, MR and Pereira, CA (2020) In silico repositioning of etidronate as a potential inhibitor of the Trypanosoma cruzi enolase. Journal of Molecular Graphics & Modelling 95, 107506.CrossRefGoogle ScholarPubMed
van Griensven, J and Diro, E (2019) Visceral leishmaniasis: recent advances in diagnostics and treatment regimens. Infectious Disease Clinics of North America 33, 79–99.CrossRefGoogle ScholarPubMed
Vazquez, C, Mejia-Tlachi, M, Gonzalez-Chavez, Z, Silva, A, Rodriguez-Zavala, JS, Moreno-Sanchez, R and Saavedra, E (2017) Buthionine sulfoximine is a multitarget inhibitor of trypanothione synthesis in Trypanosoma cruzi. FEBS Letters 591, 3881–3894.CrossRefGoogle ScholarPubMed
Vera, V, Saye, EA, Reigada, M, Damasceno, C, Silber, FS, Miranda, AM, and Pereira, MR and A, C (2016) Resveratrol inhibits Trypanosoma cruzi arginine kinase and exerts a trypanocidal activity. International Journal of Biological Macromolecules 87, 498–503.CrossRefGoogle Scholar
Villalta, F, Dobish, MC, Nde, PN, Kleshchenko, YY, Hargrove, TY, Johnson, CA, Waterman, MR, Johnston, JN and Lepesheva, GI (2013) VNI Cures acute and chronic experimental Chagas disease. Journal of Infectious Diseases 208, 504–511.CrossRefGoogle ScholarPubMed
Walvekar, P, Gannimani, R and Govender, T (2019) Combination drug therapy via nanocarriers against infectious diseases. European Journal of Pharmaceutical Sciences 127, 121–141.CrossRefGoogle ScholarPubMed
Waterhouse, A, Bertoni, M, Bienert, S, Studer, G, Tauriello, G, Gumienny, R, Heer, FT, de Beer, TAP, Rempfer, C, Bordoli, L, Lepore, R and Schwede, T (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Research 46, W296–W303.CrossRefGoogle ScholarPubMed
Webb, B and Sali, A (2016) Comparative protein structure modeling using MODELLER. Current Protocols in Protein Science 86, 2 9 1–2 9 37.CrossRefGoogle ScholarPubMed
Wiggers, HJ, Rocha, JR, Fernandes, WB, Sesti-Costa, R, Carneiro, ZA, Cheleski, J, da Silva, AB, Juliano, L, Cezari, MH, Silva, JS, McKerrow, JH and Montanari, CA (2013) Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay. PLoS Neglected Tropical Diseases 7, e2370.CrossRefGoogle ScholarPubMed
Wilkinson, SR and Kelly, JM (2009) Trypanocidal drugs: mechanisms, resistance and new targets. Expert Reviews in Molecular Medicine 11, e31.CrossRefGoogle ScholarPubMed
Wishart, DS, Feunang, YD, Guo, AC, Lo, EJ, Marcu, A, Grant, JR, Sajed, T, Johnson, D, Li, C, Sayeeda, Z, Assempour, N, Iynkkaran, I, Liu, Y, Maciejewski, A, Gale, N, Wilson, A, Chin, L, Cummings, R, Le, D, Pon, A, Knox, C and Wilson, M (2018) Drugbank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Research 46, D1074–D1082.CrossRefGoogle Scholar
Wolber, G and Langer, T (2005) Ligandscout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. Journal of Chemical Information and Modeling 45, 160–169.CrossRefGoogle ScholarPubMed
Wyatt, PG, Gilbert, IH, Read, KD and Fairlamb, AH (2011) Target validation: linking target and chemical properties to desired product profile. Current Topics in Medicinal Chemistry 11, 1275–1283.CrossRefGoogle ScholarPubMed
Wyllie, S, Patterson, S, Stojanovski, L, Simeons, FR, Norval, S, Kime, R, Read, KD and Fairlamb, AH (2012) The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Science Translational Medicine 4, 119re111.CrossRefGoogle ScholarPubMed
Wyllie, S, Brand, S, Thomas, M, Rycker, MD, Chung, C-w, Pena, I, Shishikura, Y, Spinks, D, Stojanovski, L, Thomas, J, Thompson, S, Viayna, E, Martin, J, Gray, DW, Miles, TJ, Gilbert, IH, Read, KD, Marco, M and Wyatt, PG (2019) Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition. Proceedings of the National Academy of Sciences 116, 9318–9323.CrossRefGoogle ScholarPubMed
Xu, M and Lill, MA (2013) Induced fit docking, and the use of QM/MM methods in docking. Drug Discovery Today. Technologies 10, e411–e418.CrossRefGoogle ScholarPubMed
Xue, H, Li, J, Xie, H and Wang, Y (2018) Review of drug repositioning approaches and resources. International Journal of Biological Sciences 14, 1232–1244.CrossRefGoogle ScholarPubMed
Yang, J and Zhang, Y (2015) I-TASSER server: new development for protein structure and function predictions. Nucleic Acids Research 43, W174–W181.CrossRefGoogle ScholarPubMed
Yang, X, Wu, X, Zhang, J, Zhang, X, Xu, C, Liao, S and Tu, X (2017) Recognition of hyperacetylated N-terminus of H2AZ by TbBDF2 from Trypanosoma brucei. Biochemical Journal 474, 3817–3830.CrossRefGoogle ScholarPubMed
Yap, CW (2011) PaDEL-descriptor: an open source software to calculate molecular descriptors and fingerprints. Journal of Computational Chemistry 32, 1466–1474.CrossRefGoogle ScholarPubMed
Zhou, S, Wang, F, Hsieh, TC, Wu, JM and Wu, E (2013) Thalidomide-a notorious sedative to a wonder anticancer drug. Current Medicinal Chemistry 20, 4102–4108.CrossRefGoogle ScholarPubMed
Supplementary material: File

Pereira et al. Supplementary Materials

Pereira et al. Supplementary Materials

Download Pereira et al. Supplementary Materials(File)
File 104.1 KB