title: Synthesis and biological evaluation of novel 3-O-tethered triazoles of diosgenin as potent antiproliferative agents.
abstract: Diosgenin, a promising anticancer steroidal sapogenin, was isolated from Dioscorea deltoidea. Keeping its stereochemistry rich architecture intact, a scheme for the synthesis of novel diosgenin analogues was designed using Cu (I)-catalysed alkyne-azide cycloaddition in order to study their structure-activity relationship. Both diosgenin and its analogues exhibited interesting anti-proliferative effect against four human cancer cell lines viz. HBL-100 (breast), A549 (lung), HT-29 (colon) and HCT-116 (colon) using [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide] (MTT) assay. Among the synthesized analogues, Dgn-1 bearing a simple phenyl R moiety attached via triazole to the parent molecule was identified as the most potent analogue against A549 cancer cell line having IC50of 5.54μM, better than the positive control (BEZ-235). Dgn-2 and Dgn-5 bearing o-nitrophenyl and o-cyanophenyl R moieties respectively, displayed impressive anti-proliferative activity against all the tested human cancer cell lines with IC50values ranging from 5.77 to 9.44μM. The structure-activity relationship (SAR) revealed that the analogues with simple phenyl R moiety or electron withdrawing ortho substituted R moieties seem to have beneficial impact on the anti-proliferative activity.
authors.affiliation: Department of Chemistry, National Institute of Technology, Jammu & Kashmir 190006, India; Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu & Kashmir 190005, India.
authors.lastname: Masood-Ur-Rahman
authors.affiliation: Department of Biotechnology, University of Kashmir, Jammu & Kashmir 190006, India.
authors.forename: Younis
authors.initials: Y
authors.lastname: Mohammad
authors.affiliation: Department of Biotechnology, University of Kashmir, Jammu & Kashmir 190006, India.
authors.forename: Khalid Majid
authors.initials: KM
authors.lastname: Fazili
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu & Kashmir 190005, India.
authors.forename: Khursheed Ahmad
authors.initials: KA
authors.lastname: Bhat
authors.affiliation: Department of Chemistry, National Institute of Technology, Jammu & Kashmir 190006, India. Electronic address: tabassum@nitsri.net.
authors.forename: Tabassum
authors.initials: T
authors.lastname: Ara
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D004144:Diosgenin / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D014230:Triazoles; D004144:Diosgenin
keywords: Cancer; Click chemistry; Dioscorea deltoidea; Diosgenin; Triazoles