In Vitro Antimalarial Activity of Chalcones and Their Derivatives

Rongshi Li, George L. Kenyon, Fred E. Cohen, Xiaowu Chen, Baoqing Gong, Jose N. Dominguez, Eugene Davidson, Gary Kurzban, Robert E. Miller, Edwin O. Nuzum, Philip J. Rosenthal, James H. McKerrow

Research output: Contribution to journalArticlepeer-review

379 Scopus citations

Abstract

A series of chalcones and their derivatives have been synthesized and identified as novel potential antimalarials using both molecular modeling and in vitro testing against the intact parasite. A large number of chalcones and their derivatives were prepared using one-step Claisen-Schmidt condensations of aldehydes with methyl ketones. These condensates were screened in vitro against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and shown to be active at concentrations in the nanomolar range. The most active chalcone derivative, 1-(2,5-dichlorophenyl)-3-(4-quinolinyl)-2-propen-1-one (7), had an IC50 value of 200 nM against both a chloroquine-resistant strain (W2) and a chloroquine-sensitive strain (D6). The resistance indexes for all compounds were substantially lower than for chloroquine, suggesting that this series will be active against chloroquine-resistant malaria. Structure-activity relationships (SAR) of the chalcones in the context of a homology-based model structure of the malaria trophozoite cysteine protease, the most likely target enzyme, are presented.

Original languageEnglish (US)
Pages (from-to)5031-5037
Number of pages7
JournalJournal of Medicinal Chemistry
Volume38
Issue number26
DOIs
StatePublished - Dec 1 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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