2,3-Diaryl-3 H-imidazo[4,5- b]pyridine derivatives as potential anticancer and anti-inflammatory agents

Acta Pharm Sin B. 2017 Jan;7(1):73-79. doi: 10.1016/j.apsb.2016.05.003. Epub 2016 Aug 6.

Abstract

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.

Keywords: 3H-Imidazo[4,5-b]pyri-dine; COX inhibitors; Cytotoxicity; Docking studies; MTT assay.