Design, synthesis and biological evaluation of imidazopyridine-propenone conjugates as potent tubulin inhibitors.
Sayeed IB, Lakshma Nayak V, Shareef MA, Chouhan NK, Kamal A.
A library of imidazopyridine-propenone conjugates (<b>8a-8u</b>) were synthesized and evaluated for their antitumor activity against four human cancer cell lines, namely, prostate (DU-145), lung (A549), cervical (Hela) and breast (MCF-7) cancer cell lines. These conjugates showed good to moderate activity against the tested cell lines. Among them, two conjugates (<b>8m</b> and <b>8q</b>) showed significant antiproliferative activity against the human lung cancer cell line (A549) with IC<sub>50</sub> values of 0.86 μM and 0.93 μM, respectively. Flow cytometry analysis revealed that these compounds arrested the cell cycle at the G<sub>2</sub>/M phase in the human lung cancer cell line (A549), inhibiting tubulin polymerization leading to apoptosis. Further, Hoechst staining, decrease in mitochondrial membrane potential and Annexin V-FITC assay suggested that the cell death was due to apoptosis induction. Overall, the present investigation demonstrated that the synthesized imidazopyridine-propenone conjugates are promising tubulin inhibitors and apoptotic inducers.