title: Discovery of 3,3'-diindolylmethanes as potent antileishmanial agents.
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.
authors.affiliation: Medicinal Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India. sbharate@iiim.ac.in
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Bharate
authors.forename: Jaideep B
authors.initials: JB
authors.lastname: Bharate
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mudududdla
authors.forename: Rammohan R
authors.initials: RR
authors.lastname: Yadav
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.forename: P R
authors.initials: PR
authors.lastname: Sharma
authors.forename: Sudip
authors.initials: S
authors.lastname: Maity
authors.forename: Baldev
authors.initials: B
authors.lastname: Singh
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology; D008956:Models, Chemical; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D007211:Indoles; C016392:3,3'-diindolylmethane