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In vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine Mannich base derivatives

  • ALVARO MARTIN-MONTES (a1), MERY SANTIVAÑEZ-VELIZ (a2) (a3), ELSA MORENO-VIGURI (a2) (a3), RUBÉN MARTÍN-ESCOLANO (a1), CARMEN JIMÉNEZ-MONTES (a1), CATALINA LOPEZ-GONZALEZ (a1), CLOTILDE MARÍN (a1), CARMEN SANMARTÍN (a2) (a3), RAMÓN GUTIÉRREZ SÁNCHEZ (a4), MANUEL SÁNCHEZ-MORENO (a1) and SILVIA PÉREZ-SILANES (a2) (a3)...

Summary

Leishmaniasis is one of the world's most neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, we present 20 arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against Trypanosoma cruzi that have now been studied against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani and Leishmania braziliensis strains. Six out of the 20 Mannich base-type derivatives showed Selectivity Index between 39 and 2337 times higher in the amastigote form than the reference drug glucantime. These six derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at an IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing a greater alteration in glucose catabolism and leading to greater levels of iron superoxide dismutase inhibition. These molecules could be potential candidates for leishmaniasis chemotherapy.

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Corresponding author

*Corresponding authors: Facultad de Farmacia y Nutrición, Departamento de Química Orgánica y Farmacéutica, Universidad de Navarra, Campus Universitario, 31008 Pamplona, Spain. E-mail: sperez@unav.es and Facultad de Ciencias, Departamento de Parasitología, Universidad de Granada, 18071 Granada, Spain. E-mail: msanchem@ugr.es

References

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In vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine Mannich base derivatives

  • ALVARO MARTIN-MONTES (a1), MERY SANTIVAÑEZ-VELIZ (a2) (a3), ELSA MORENO-VIGURI (a2) (a3), RUBÉN MARTÍN-ESCOLANO (a1), CARMEN JIMÉNEZ-MONTES (a1), CATALINA LOPEZ-GONZALEZ (a1), CLOTILDE MARÍN (a1), CARMEN SANMARTÍN (a2) (a3), RAMÓN GUTIÉRREZ SÁNCHEZ (a4), MANUEL SÁNCHEZ-MORENO (a1) and SILVIA PÉREZ-SILANES (a2) (a3)...

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