Hostname: page-component-76fb5796d-vfjqv Total loading time: 0 Render date: 2024-04-26T13:48:19.326Z Has data issue: false hasContentIssue false

Effect of a newly synthesized quinoline-based compound (PPQ-8) on murine schistosomiasis mansoni

Published online by Cambridge University Press:  07 February 2020

A. Taman*
Affiliation:
Department of Medical Parasitology, Mansoura University, Mansoura35516, Egypt
S.M. Alhusseiny
Affiliation:
Department of Medical Parasitology, Mansoura University, Mansoura35516, Egypt
N.E. Saleh
Affiliation:
Department of Medical Parasitology, Mansoura University, Mansoura35516, Egypt
M.Y. Youssef
Affiliation:
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura35516, Egypt
B. Mansour
Affiliation:
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Mansoura, Egypt
M. Massoud
Affiliation:
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt
S.N. El-Beshbishi
Affiliation:
Department of Medical Parasitology, Mansoura University, Mansoura35516, Egypt
*
Author for correspondence: A. Taman, E-mail: amirataman@mans.edu.eg; amira.taman@mail.mcgill.ca

Abstract

Schistosomiasis represents a public health problem and praziquantel is the only drug used for treatment of all forms of the disease. Thus, the development of new anti-schistosomal agents is of utmost importance to increase the effectiveness, reduce side effects and delay the emergence of resistance. The present study was conducted to report the therapeutic efficacy of PPQ-8, a new synthetic quinoline-based compound against Schistosoma mansoni. Mice were treated with PPQ-8 at day 49 post infection using two treatment regimens (20 and 40 mg/kg). Significant reductions were recorded in hepatic (62.9% and 83.6%) and intestinal tissue egg load (57.4% and 73.5%), granuloma count (75.4% and 89.1%) and diameter (26.2% and 47.3%), in response to the drug regimens, respectively. In addition, both treatment regimens induced significant decrease in liver (23.3% and 32.8%) and spleen (37.5% and 45.3%) indices. Also, there were significant reductions in mature ova, total worm and female count, which were more prominent with the higher dose. The reduction in the level of nitric oxide in the liver by both therapeutic regimens to 22.5% and 47.2% indicates the anti-oxidant activity of PPQ-8. Bright field microscopic examination of worms recovered from infected and PPQ-8-treated mice showed nearly empty intestinal caeca with no observable changes in the tegument. Our findings hold promise for the development of a novel anti-schistosomal drug using PPQ-8, but further in vitro and in vivo studies are needed to elucidate the possible mechanism/s of action and to study the effect of PPQ-8 on other human schistosomes.

Type
Research Paper
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

Abd Elgawad, H, Alhusseiny, SM, Taman, A, et al. (2019) Biological evaluation of newly synthesized quinoline-based compound PPQ-8 in acute and chronic toxoplasmosis: an experimental study. Experimental Parasitology 206, 107756.CrossRefGoogle Scholar
Aleixo de Carvalho, LS, Geraldo, RB, de Moraes, J, et al. (2015) Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae). Experimental Parasitology 159, 207214.CrossRefGoogle Scholar
Aragon, AD, Imani, RA, Blackburn, VR, et al. (2008) Microarray based analysis of temperature and oxidative stress induced messenger RNA in Schistosoma mansoni. Molecular and Biochemical Parasitology 162, 134141.CrossRefGoogle ScholarPubMed
Banks, WA (2009) Characteristics of compounds that cross the blood-brain barrier. BMC Neurology 9(Suppl 1), S3.CrossRefGoogle ScholarPubMed
Bengtsson, AA, Sturfelt, G, Lood, C, et al. (2012) Pharmacokinetics, tolerability, and preliminary efficacy of paquinimod (ABR-215757), a new quinoline-3-carboxamide derivative: studies in lupus-prone mice and a multicenter, randomized, double-blind, placebo-controlled, repeat-dose, dose-ranging study in patients with systemic lupus erythematosus. Arthritis & Rheumatism 64, 15791588.CrossRefGoogle Scholar
Berhe, N, Myrvang, B and Gundersen, SG (2008) Reversibility of schistosomal periportal thickening/fibrosis after praziquantel therapy: a twenty-six month follow-up study in Ethiopia. American Journal of Tropical Medicine and Hygiene 78, 228234.CrossRefGoogle ScholarPubMed
Cheever, AW (1968) Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting Schistosoma mansoni eggs in tissues. Bulletin of the World Health Organization 39, 328331.Google ScholarPubMed
Chen, MM, Shi, L and Sullivan, DJ Jr (2001) Haemoproteus and Schistosoma synthesize heme polymers similar to Plasmodium hemozoin and beta-hematin. Molecular Biochemistry and Parasitology 113, 18.CrossRefGoogle ScholarPubMed
Cioli, D, Pica-Mattoccia, L, Basso, A, et al. (2014) Schistosomiasis control: praziquantel forever? Molecular Biochemistry and Parasitology 195, 23–9.CrossRefGoogle ScholarPubMed
Corrêa Soares, JB, Menezes, D, Vannier-Santos, MA, et al. (2009) Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Neglected Tropical Diseases 3, e477.CrossRefGoogle ScholarPubMed
de Moraes, J (2015) Natural products with antischistosomal activity. Future Medicinal Chemistry 7, 801820.CrossRefGoogle ScholarPubMed
El-Ahl, SA, Hegazi, MA, Mahmoud, M, et al. (2013) Parasitological changes within experimentally murine schistosomiasis mansoni upon treatment by somatostatin, artemether and their combination. Research Journal of Parasitology 8, 113.Google Scholar
El-Beshbishi, SN, Taman, A, El-Malky, M, et al. (2013a) First insight into the effect of single oral dose therapy with artemisinin-naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection. International Journal for Parasitology 43, 521530.CrossRefGoogle Scholar
El-Beshbishi, SN, Taman, A, El-Malky, M, et al. (2013b) In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain. Experimental Parasitology 135, 240245.CrossRefGoogle Scholar
El-Beshbishi, SN, Saleh, NE, Abd El-Mageed, S, et al. (2019) Effect of omega-3 fatty acids administered as monotherapy or combined with artemether on experimental Schistosoma mansoni infection. Acta Tropica 194, 6268.CrossRefGoogle ScholarPubMed
El Bialy, SA, Taman, A, El-Beshbishi, SN, et al. (2013) Effect of a novel benzimidazole derivative in experimental Schistosoma mansoni infection. Parasitology Research 112, 42214229.CrossRefGoogle ScholarPubMed
Fahmy, SR, Rabia, I and Mansour, EM (2014) The potential role of mefloquine against Schistosoma mansoni infection by prohibition of hepatic oxidative stress in mice. The Journal of Basic and Applied Zoology 67, 4047.CrossRefGoogle Scholar
Fan, YL, Wu, JB, Cheng, XW, Zhang, FZ and Feng, LS (2018a) Fluoroquinolone derivatives and their anti-tubercular activities. European Journal of Medicinal Chemistry 146, 554563.CrossRefGoogle Scholar
Fan, YL, Cheng, XW, Wu, JB, Liu, M, Zhang, FZ, Xu, Z and Feng, LS (2018b) Antiplasmodial and antimalarial activities of quinolone derivatives: an overview. European Journal of Medicinal Chemistry 146, 114.CrossRefGoogle Scholar
Foley, M and Tilley, L (1998) Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacology and Therapeutics 79, 5587.CrossRefGoogle ScholarPubMed
Freitas, CRL, Barbosa, AA Jr, Fernandes, ALM and Andrade, ZA (1999) Pathology of the spleen in hepatosplenic schistosomiasis. Morphometric evaluation and extracellular matrix changes. Memórias do Instituto Oswaldo Cruz 94, 815822.CrossRefGoogle ScholarPubMed
Friedman, JF, Olveda, RM, Mirochnick, MH, et al. (2018) Praziquantel for the treatment of schistosomiasis during human pregnancy. Bulletin of the World Health Organization 96, 5965.CrossRefGoogle ScholarPubMed
Hoffmann, KF, Wynn, TA and Dunne, DW (2002) Cytokine-mediated host responses during schistosome infections; walking the fine line between immunological control and immunopathology. Advances in Parasitology 252, 265307.CrossRefGoogle Scholar
Kamel, IA, Cheever, AW, Elwi, AM, et al. (1977) Schistosoma mansoni and S. haematobium infections in Egypt. I. Evaluation of techniques for recovery of worms and eggs at necropsy. American Journal of Tropical Medicine and Hygiene 26, 696701.CrossRefGoogle ScholarPubMed
Keiser, J, Chollet, J, Xiao, SH, et al. (2009) Mefloquine–an aminoalcohol with promising antischistosomal properties in mice. PLoS neglected tropical diseases 3, e350.CrossRefGoogle Scholar
Lawrence, JD (1973) The ingestion of red blood cells by Schistosoma mansoni. The Journal of Parasitology 59, 6063.CrossRefGoogle ScholarPubMed
Li, HJ, Wang, W, Qu, GL, et al. (2012) Effect of the in vivo activity of dihydroartemisinin against Schistosoma mansoni infection in mice. Parasitology Research 110, 17271732.CrossRefGoogle ScholarPubMed
Luo, ZG, Tan, JJ, Zeng, Y, et al. (2010) Development of integrase inhibitors of quinolone acid derivatives for treatment of AIDS: an overview. Mini-Reviews in Medicinal Chemistry 10, 10461057.CrossRefGoogle ScholarPubMed
Magwere, T, Naik, YS and Hasler, JA (1997) Effects of chloroquine treatment on antioxidant enzymes in rat liver and kidney. Free Radical Biology and Medicine 22, 321327.CrossRefGoogle ScholarPubMed
Manneck, T, Haggenmuller, Y and Keiser, J (2010) Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes of Schistosoma mansoni. Parasitology 137, 8598.CrossRefGoogle ScholarPubMed
Merrifield, M, Hotez, PJ, Beaumier, CM, et al. (2016) Advancing a vaccine to prevent human schistosomiasis. Vaccine 34, 29882991.CrossRefGoogle ScholarPubMed
Moreira, LSA, Piló-Veloso, D, de Mello, RT, et al. (2007) A study of the activity of 2-(alkylamino)-1-phenyl-1-ethanethiosulfuric acids against infection by Schistosoma mansoni in a murine model. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 385390.CrossRefGoogle Scholar
Muruganantham, N, Sivakumar, R, Anbalagan, N, Gunasekaran, V and Leonard, JT (2004) Synthesis, anticonvulsant and antihypertensive activities of 8-substituted quinoline derivatives. Biological and Pharmaceutical Bulletin 27, 16831687.CrossRefGoogle ScholarPubMed
Musiol, R, Jampilek, J, Buchta, V, et al. (2006) Antifungal properties of new series of quinoline derivatives. Bioorganic and Medicinal Chemistry 14, 35923598.CrossRefGoogle ScholarPubMed
Oliveira, MF, d'Avila, JCP, Torres, CR, et al. (2000) Haemozoin in Schistosoma mansoni. Molecular and Biochemical Parasitology 111, 217221.CrossRefGoogle ScholarPubMed
Oliveira, MF, Timm, BL, Machado, EA, et al. (2002) On the pro-oxidant effects of haemozoin. FEBS Letter 512, 139144.CrossRefGoogle ScholarPubMed
Oliveira, MF, d'Avila, JC, Tempone, AJ, et al. (2004) Inhibition of heme aggregation by chloroquine reduces Schistosoma mansoni infection. The Journal of Infectious Diseases 190, 843852.CrossRefGoogle ScholarPubMed
Olveda, DU, McManus, DP and Ross, AG (2016) Mass drug administration and the global control of schistosomiasis: successes, limitations and clinical outcomes. Current Opinion in Infectious Diseases 29, 595608.CrossRefGoogle ScholarPubMed
Pellegrino, J, Oliveira, CA, Faria, J and Cunha, AS (1962) New approach to the screening of drugs in experimental schistosomiasis mansoni in mice. American Journal of Tropical Medicine and Hygiene 11, 201215.CrossRefGoogle ScholarPubMed
Rajesh, YBRD (2018) Quinoline heterocycles: synthesis and bioactivity. In Nandeshwarappa BP and Sadashiv SO (eds), Heterocycles-synthesis and biological activities. IntechOpen. Available at https://www.intechopen.com/online-first/quinoline-heterocycles-synthesis-and-bioactivity (accessed 1 September 2019).Google Scholar
Seif el-Din, SH, Al-Hroob, AM and Ebeid, FA (2011) Schistosoma mansoni: N-acetylcysteine downregulates oxidative stress and enhances the antischistosomal activity of artemether in mice. Experimental Parasitology 128, 230235.CrossRefGoogle ScholarPubMed
Sharma, PC, Monika, C, Archana, S, et al. (2013) Insight view on possible role of fluoroquinolones in cancer therapy. Current Topics in Medicinal Chemistry 13, 20762096.CrossRefGoogle ScholarPubMed
Skelly, PJ and Alan Wilson, R (2006) Making sense of the schistosome surface. Advances in Parasitology 63, 185284.CrossRefGoogle ScholarPubMed
Smithers, SR and Terry, RJ (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology 55, 695700.CrossRefGoogle ScholarPubMed
Spivak, AY, Keiser, J, Vargas, M, et al. (2014) Synthesis and activity of new triphenylphosphonium derivatives of betulin and betulinic acid against Schistosoma mansoni in vitro and in vivo. Bioorganic and Medicinal Chemistry 22, 62976304.CrossRefGoogle ScholarPubMed
Taman, A, El-Beshbishi, S, El-Tantawy, N, El-Hawary, A and Azab, M (2014) Evaluation of the in vivo effect of ivermectin on Schistosoma mansoni in experimentally-infected mice. Journal of Coastal Life Medicine 2, 817823.Google Scholar
Taman, A, El-Beshbishi, SN, Bardicy, SE, et al. (2016) In vitro screening of BTP-Iso on Schistosoma mansoni and its intermediate host Biomphalaria alexandrina. Asian Pacific Journal of Tropical Disease 6, 946951.CrossRefGoogle Scholar
Tielens, AG (1994) Energy generation in parasitic helminths. Parasitology Today 10, 346352.CrossRefGoogle ScholarPubMed
Upadhyay, KD, Dodia, NM, Khunt, RC, Chaniara, RS and Shah, AK (2018) Synthesis and biological screening of Pyrano[3,2-c]quinoline analogues as anti-inflammatory and anticancer agents. ACS Medicinal Chemistry Letters 9, 283288.CrossRefGoogle ScholarPubMed
Utzinger, J, Chollet, J, Tu, Z, Xiao, S and Tanner, M (2002) Comparative study of the effects of artemether and artesunate on juvenile and adult Schistosoma mansoni in experimentally infected mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 96, 318323.CrossRefGoogle ScholarPubMed
Wang, Z, Hu, J, Yang, X, Feng, X, Li, X, Huang, L and Chan, ASC (2018) Design, synthesis, and evaluation of orally bioavailable quinoline-indole derivatives as innovative multitarget-directed ligands: promotion of cell proliferation in the adult murine hippocampus for the treatment of Alzheimer's disease. Journal of Medicinal Chemistry 61, 18711894.CrossRefGoogle ScholarPubMed
Wang, J, Zhou, H, Zheng, J, et al. (2006) The antimalarial artemisinin synergizes with antibiotics to protect against lethal live Escherichia coli challenge by decreasing proinflammatory cytokine release. Antimicrobial Agents and Chemotherapy 50, 24202427.CrossRefGoogle ScholarPubMed
Wilhelm, EA, Ferreira, AT, Pinz, MP, et al. (2017) Antioxidant effect of quinoline derivatives containing or not selenium: relationship with antinociceptive action quinolines are antioxidant and antinociceptive. Anais da Academia Brasileira de Ciências 89, 457467.CrossRefGoogle ScholarPubMed
Yang, NJ and Hinner, MJ (2015) Getting across the cell membrane: an overview for small molecules, peptides, and proteins. Methods in Molecular Biology 1266, 2953.CrossRefGoogle ScholarPubMed
Zhang, Z, Xiao, X, Su, T, et al. (2017) Synthesis, structure-activity relationships and preliminary mechanism of action of novel water-soluble 4-quinolone-3-carboxamides as antiproliferative agents. European Journal of Medicinal Chemistry 140, 239251.CrossRefGoogle ScholarPubMed
Zhang, GF, Zhang, S, Pan, B, et al. (2018) 4-Quinolone derivatives and their activities against Gram positive pathogens. European Journal of Medicinal Chemistry 143, 710723.CrossRefGoogle ScholarPubMed