Antimalarial activity of thiosemicarbazones and purine derived nitriles

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Mallari, Jeremy P.^1,2  Guiguemde, Wendyam A.¹  Guy, R. Kiplin¹ 

[1] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA

[2] Univ Calif San Francisco, Grad Program Chem & Chem Biol, San Francisco, CA 94143 USA

关键词: Malaria;    Cysteine protease inhibitor;    Falcipain;    Thiosemicarbazone;    Purine nitrile;   

DOI  :  10.1016/j.bmcl.2009.04.142

来源: Elsevier

【 摘 要 】

Malaria is a devastating illness caused by multiple species of the Plasmodium genus. The parasite's falcipain proteases have been extensively studied as potential drug targets. Here we report the testing of two established cysteine protease inhibitor scaffolds against both chloroquine sensitive and chloroquine resistant parasites. A subset of purine derived nitriles killed the parasite with moderate potency, and these inhibitors do not seem to exert their antiproliferative effects as cysteine protease inhibitors. Compound potency was determined to be similar against both parasite strains, indicating a low probability of cross resistance with chloroquine. These compounds represent a novel antimalarial scaffold, and a potential starting point for the development new inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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