Discovery of 3,3 %26apos;-diindolylmethanes as potent antileishmanial agents

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

来源：European Journal of Medicinal Chemistry, 2013, 63: 435-443.

DOI：10.1016/j.ejmech.2013.02.024

• 3,3 %26apos
• -Diindolylmethanes
• Antileishmanial
• Antimalarial
• Leishmania donovani
• Antifungal
• Fe-pillared interlayered clay

An efficient protocol for synthesis of 3,3%26apos;-diindolylmethanes using recyclable Fe-pillared interlayered clay (Fe-PILC) catalyst under aqueous medium has been developed. All synthesized 3,3%26apos;-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%26apos;-diindolylmethane 8g was found to be the most potent antileishmanial analog showing IC50 values of 7.88 and 8.37 mu M 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%26apos;-diindolylmethanes essential for potent antileishmanial activity. These compounds also exhibited promising antifungal activity against Cryptococcus neoformans, wherein fluorophenyl substituted 3,3%26apos;-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%26apos;-diindolylmethane class of compounds.

• 出版日期2013-5