Discovery of 3,3′-diindolylmethanes as potent antileishmanial agents

Sandip B. Bharate, Jaideep B. Bharate, Shabana I. Khan, Babu L. Tekwani, Melissa R. Jacob, Ramesh Mudududdla, Rammohan R. Yadav, Baljinder Singh, P. R. Sharma, Sudip Maity, Baldev Singh, Ikhlas A. Khan, Ram A. Vishwakarma

Research output: Contribution to journalArticleResearchpeer-review

58 Citations (Scopus)

Abstract

An efficient protocol for synthesis of 3,3′-diindolylmethanes using recyclable Fe-pillared interlayered clay (Fe-PILC) catalyst under aqueous medium has been developed. All synthesized 3,3′-diindolylmethanes showed promising antileishmanial activity against Leishmania donovani promastigotes as well as axenic amastigotes. Structure-activity relationship analysis revealed that nitroaryl substituted diindolylmethanes showed potent antileishmanial activity. The 4-nitrophenyl linked 3,3′-diindolylmethane 8g was found to be the most potent antileishmanial analog showing IC50 values of 7.88 and 8.37 μM against both L. donovani promastigotes and amastigotes, respectively. Further, a pharmacophore based QSAR model was established to understand the crucial molecular features of 3,3′-diindolylmethanes essential for potent antileishmanial activity. These compounds also exhibited promising antifungal activity against Cryptococcus neoformans, wherein fluorophenyl substituted 3,3′-diindolylmethanes were found to be most potent antifungal agents. Developed synthetic protocol will be useful for economical and eco-friendly synthesis of potent antileishmanial and antifungal 3,3′-diindolylmethane class of compounds.

Original languageEnglish
Pages (from-to)435-443
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume63
DOIs
Publication statusPublished - 21 Mar 2013
Externally publishedYes

Keywords

  • 3,3′-Diindolylmethanes
  • Antifungal
  • Antileishmanial
  • Antimalarial
  • Fe-pillared interlayered clay
  • Leishmania donovani

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