Antimalarial activity of thiosemicarbazones and purine derived nitriles

Jeremy P. Mallari, Wendyam A. Guiguemde, R. Kiplin Guy

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3546-3549
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number13
DOIs
StatePublished - Jul 1 2009

Bibliographical note

Funding Information:
This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children’s Research Hospital, NIH Grant AI075517.

Keywords

  • Cysteine protease inhibitor
  • Falcipain
  • Malaria
  • Purine nitrile
  • Thiosemicarbazone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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