Article
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria.
Science (New York, N.Y.) - 27 Sept 2024
Chahine Z, Abel S, Hollin T, Barnes G L, Chung J H, Daub M E, Renard I, Choi J Y, Vydyam P, Pal A, Alba-Argomaniz M, Banks C A S, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M C, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C J, Bei A K, Florens L, Ben Mamoun C, Vanderwal C D, Le Roch K G
Abstract excerpt
We report the discovery of MED6-189, an analog of the kalihinol family of isocyanoterpene natural products that is effective against drug-sensitive and drug-resistant Plasmodium falciparum strains, blocking both asexual replication and sexual differentiation. In vivo studies using a humanized mouse model of malaria confirm strong efficacy of the compound in animals with no apparent hemolytic activity or toxicity....
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