Design and synthesis of novel 1,2,3-triazole derivatives of coronopilin as anti-cancer compounds

Eur J Med Chem. 2014 Jul 23:82:255-62. doi: 10.1016/j.ejmech.2014.05.053. Epub 2014 May 24.

Abstract

A series of 1,2,3-triazole coronopilin congeners have been designed and synthesized by employing click chemistry approach starting from parthenin and evaluated for their cytotoxicity against a panel of six human cancer cell lines (PC-3, THP-1, HCT-15, HeLa, A-549 and MCF-7). While many compounds exhibited significant anticancer activity, compound 3a, was found to be the most promising analogue in this series with IC50 values of 3.1 μM on PC-3 cell line. Flow-cytometric studies showed that 1,2,3-triazole derivative-3a induce dose dependent apoptosis in the sub G1 phase. This lead molecule-3a was further studied for NF-κB (p65) transcription factor inhibitory activity using Elisa and western blotting analysis which confirmed concentration dependent inhibitory activity against NF-κB, p65 with 80% inhibition in 24 h at 100 μM.

Keywords: 1,2,3-Triazole; Coronopilin; NF-κB (p65) inhibitors; Parthenin; Sesquiterpenoid lactone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Azulenes / chemical synthesis
  • Azulenes / chemistry
  • Azulenes / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Azulenes
  • Sesquiterpenes
  • Triazoles
  • coronopilin