Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen

Nature Communications
Celia Miguel-BlancoEsperanza Herreros

Abstract

Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay (Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities <2 μM, chemically classified into 57 clusters and 33 singletons. Up to 68% of the hits are chemotypes described for the first time as late-stage gametocyte-targeting molecules. In addition, the biological profile of 90 compounds representing the chemical diversity is assessed. We confirm in vitro transmission-blocking activity of four of the six selected molecules belonging to three distinct scaffold clusters. Overall, this TCAMS gametocyte screen provides 276 promising antimalarial molecules with dual asexual/sexual activity, representing starting points for target identification and candidate selection.

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Citations

Mar 11, 2020·Antimicrobial Agents and Chemotherapy·Mark D WilkinsonJake Baum
Jul 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Laura A KirkmanGang Lin
Sep 23, 2020·Pharmaceuticals·Phanankosi MoyoLyn-Marié Birkholtz
Jul 17, 2021·Frontiers in Cellular and Infection Microbiology·Ashleigh van HeerdenLyn-Marie Birkholtz
Aug 7, 2019·Journal of Medicinal Chemistry·Trent D AshtonBrad E Sleebs

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Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.