Triazole tethered C5-curcuminoid-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies

Harbinder Singh, Mandeep Kumar, Kunal Nepali, Manish K. Gupta, Ajit K. Saxena, Sahil Sharma, Preet Mohinder S. Bedi

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Keeping in view the confines allied with presently accessible antitumor agents and success of C5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin.

Original languageEnglish
Pages (from-to)102-115
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume116
DOIs
Publication statusPublished - Jun 30 2016
Externally publishedYes

Keywords

  • Antitubulin
  • Antitumor
  • C-curcuminoid
  • Coumarin
  • Docking
  • Hybrid

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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