An Antiparasitic Compound from the Medicines for Malaria Venture Pathogen Box Promotes Leishmania Tubulin Polymerization.

ABSTRACT: The few frontline antileishmanial drugs are poorly effective and toxic. To search for new drugs for this neglected tropical disease, we tested the activity of compounds in the Medicines for Malaria Venture (MMV) "Pathogen Box" against Leishmania amazonensis axenic amastigotes. Screening yielded six discovery antileishmanial compounds with EC₅₀ values from 50 to 480 nM. Concentration-response assays demonstrated that the best hit, MMV676477, had mid-nanomolar cytocidal potency against intracellular Leishmania amastigotes, Trypanosoma brucei, and Plasmodium falciparum, suggesting broad antiparasitic activity. We explored structure-activity relationships (SAR) within a small group of MMV676477 analogs and observed a wide potency range (20-5000 nM) agains

SUBMITTER: Ullah I 

PROVIDER: S-EPMC8059355 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature