Design, synthesis and biological evaluation of novel thiazole-naphthalene derivatives as potential anticancer agents and tubulin polymerisation inhibitors

A novel series of thiazole-naphthalene derivatives as tubulin polymerisation inhibitors were designed, synthesised, and evaluated for the anti-proliferative activities. The majority of the tested compounds exhibited moderate to potent antiproliferative activity on the MCF-7 and A549 cancer cell lines. Among them, compound 5b was found to be the most active compound with IC50 values of 0.48 +/- 0.03 and 0.97 +/- 0.13 mu M. Moreover, mechanistic studies revealed that 5b significantly inhibited tubulin polymerisation with an IC50 value of 3.3 mu M, as compared to the standard drug colchicine (IC50 = 9.1 mu M). Further cellular mechanism studies elucidated that 5b arrested the cell cycle at G2/M phase and induced apoptosis in MCF-7 cancer cells. Molecular modelling study indicated that 5b binds well to the colchicine binding site of tubulin. In summary, these results suggest that 5b represents a promising tubulin polymerisation inhibitor worthy of further investigation as potential anticancer agents.

Automated summary

A novel series of thiazole-naphthalene derivatives were designed, synthesised, and evaluated for their anti-proliferative activities. Among them, compound 5b showed the highest activity as a tubulin polymerisation inhibitor, inducing apoptosis in cancer cells by arresting the cell cycle at G2/M phase.