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Synthesis and insight into the structure-activity relationships of chalcones as antimalarial agents.

Authors
  • Tadigoppula, Narender
  • Korthikunta, Venkateswarlu
  • Gupta, Shweta
  • Kancharla, Papireddy
  • Khaliq, Tanvir
  • Soni, Awakash
  • Srivastava, Rajeev Kumar
  • Srivastava, Kumkum
  • Puri, Sunil Kumar
  • Raju, Kanumuri Siva Rama
  • Sijwali, Puran Singh
  • Kumar, Vikash
  • Mohammad, Imran Siddiqi
Type
Published Article
Journal
Journal of Medicinal Chemistry
Publisher
American Chemical Society
Publication Date
Jan 10, 2013
Volume
56
Issue
1
Pages
31–45
Identifiers
DOI: 10.1021/jm300588j
PMID: 23270565
Source
Medline
License
Unknown

Abstract

Licochalcone A (I), isolated from the roots of Chinese licorice, is the most promising antimalarial compound reported so far. In continuation of our drug discovery program, we isolated two similar chalcones, medicagenin (II) and munchiwarin (III), from Crotalaria medicagenia , which exhibited antimalarial activity against Plasmodium falciparum . A library of 88 chalcones were synthesized and evaluated for their in vitro antimalarial activity. Among these, 67, 68, 74, 77, and 78 exhibited good in vitro antimalarial activity against P. falciparum strains 3D7 and K1 with low cytotoxicity. These chalcones also showed reduction in parasitemia and increased survival time of Swiss mice infected with Plasmodium yoelii (strain N-67). Pharmacokinetic studies indicated that low oral bioavailability due to poor ADME properties. Molecular docking studies revealed the binding orientation of these inhibitors in active sites of falcipain-2 (FP-2) enzyme. Compounds 67, 68, and 78 showed modest inhibitory activity against the major hemoglobin degrading cysteine protease FP-2.

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