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

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.

• Authors: Jabeena Khazir, Irfan Hyder, J Laxmi Gayatri, Leela Prasad Yandrati, Naresh Nalla, Gousia Chasoo, Ajay Mahajan, A K Saxena, M S Alam, G N Qazi, Halmuthur M Sampath Kumar
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 82 Pg. 255-62 (Jul 23 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 24910974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Azulenes
• Sesquiterpenes
• Triazoles
• coronopilin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Azulenes (chemical synthesis, chemistry, 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, chemistry, pharmacology)
• Structure-Activity Relationship
• Triazoles (chemical synthesis, chemistry, pharmacology)