Antimalarial activity of thiosemicarbazones and purine derived nitriles.
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.
Mallari
Jeremy P
JP
Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, CA 94143-2280, USA.
Guiguemde
Wendyam A
WA
Guy
R Kiplin
RK
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D009570:Nitriles / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D009570:Nitriles; D011687:Purines; D013882:Thiosemicarbazones