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.
Jabeena Khazir  1 ,  Irfan Hyder  2 ,  J Laxmi Gayatri  2 ,  Leela Prasad Yandrati  2 ,  Naresh Nalla  2 ,  Gousia Chasoo  1 ,  Ajay Mahajan  1 ,  A K Saxena  1 ,  M S Alam  3 ,  G N Qazi  3 ,  Halmuthur M Sampath Kumar  4
Affiliations
  • 1. Medicinal Chemistry Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India.
  • 2. Natural Products Chemistry Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 3. Department of Chemistry, Jamia Hamdard University, New Delhi 110062, India.
  • 4. Natural Products Chemistry Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: [email protected].
PMID: 24910974 DOI: 10.1016/j.ejmech.2014.05.053
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.