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

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.

Graphical abstractAn efficient protocol for synthesis of 3,3′-diindolylmethanes using recyclable Fe-PILC catalyst has been developed. 3,3′-Diindolylmethanes showed promising antileishmanial activity against Leishmania donovani promastigotes.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We report discovery of 3,3′-diindolylmethanes as a new class of antileishmanial agents. ► Nitrofuryl linked 3,3′-diindolylmethane is most potent antileishmanial compound. ► An efficient protocol for synthesis of 3,3′-diindolylmethanes using recyclable Fe-PILC catalyst is described. ► Detailed SAR and pharmacophore based QSAR has been investigated. ► Promising antifungal activity against Cryptococcus neoformans was also observed.