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Discovering the seeds for new drugs that target the neglected tropical disease leishmaniasis

Ayotte, Yann; Descoteaux, Albert; Laplante, Steven . Discovering the seeds for new drugs that target the neglected tropical disease leishmaniasis In: 16e symposium annuel de parasitologie moléculaire du Québec, 6-7 juin 2016, Université McGill, Montréal, QC.

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Résumé

The current treatment of leishmaniasis essentially relies on chemotherapy and as to date, no therapeutic or preventive vaccines are available. To this day, treatment failure, toxicity, emergence of drug resistance and the cost of current medication stresses the need for alternative treatments. We therefore screened a library of 1604 compounds in order to see if some of them showed a leishmanicidal effect. This phenotype screen identified three structurally-related compounds which showed an inhibitory effect on L. amazonensis infected macrophages without signs of toxicity to macrophages. A dose-response effect was observed and IC50s of 128, 80 and 35 μM were obtained for P1C2, MAGA-005 and MAGA-008 compounds respectively. Since Leishmania survival within macrophages depends on the capacity of amastigotes parasites to resist or evade the host cytotoxic activities, nitric oxide (NO) and TNF levels were measured to see if the molecules exercised their leishmanicidal effect indirectly by conferring leishmanicidal activities to infected macrophages. No consistent effects were observed on NO and TNF. Therefore, the inhibitory effect likely comes from a direct interaction of the compounds with the parasite. Current efforts are to identify the parasite target and improve activity and selectivity of the current series of compounds.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Présentation par affiche
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 mai 2018 20:52
Dernière modification: 01 mai 2018 20:52
URI: http://espace.inrs.ca/id/eprint/7080

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