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

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 36; no. 1; pp. 1693 - 1701
• Main Authors: Wang, Guangcheng, Liu, Wenjing, Fan, Meiyan, He, Min, Li, Yongjun, Peng, Zhiyun
• Format: Journal Article
• Language: English
• Published: ABINGDON Taylor & Francis 01.01.2021; Taylor & Francis Group
• Subjects: anticancer; Biochemistry & Molecular Biology; Brief Report; Chemistry, Medicinal; Life Sciences & Biomedicine; naphthalene; Pharmacology & Pharmacy; Science & Technology; Short Communication; thiazole; tubulin; tubulin polymerisation; naphthalene; MICROTUBULES; tubulin; tubulin polymerisation; Thiazole; MOLECULAR DOCKING; anticancer; HYBRIDS
• ISSN: 1475-6366; 1475-6374; 1475-6374
• DOI: 10.1080/14756366.2021.1958213

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.