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Steroids. 2017 Feb;118:1-8. doi: 10.1016/j.steroids.2016.11.003. Epub 2016 Nov 15.

Synthesis and biological evaluation of novel 3-O-tethered triazoles of diosgenin as potent antiproliferative agents.

Author information

1
Department of Chemistry, National Institute of Technology, Jammu & Kashmir 190006, India; Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu & Kashmir 190005, India.
2
Department of Biotechnology, University of Kashmir, Jammu & Kashmir 190006, India.
3
Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu & Kashmir 190005, India.
4
Department of Chemistry, National Institute of Technology, Jammu & Kashmir 190006, India. Electronic address: tabassum@nitsri.net.

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 IC50 of 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 IC50 values 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.

KEYWORDS:

Cancer; Click chemistry; Dioscorea deltoidea; Diosgenin; Triazoles

PMID:
27864018
DOI:
10.1016/j.steroids.2016.11.003
[Indexed for MEDLINE]

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