Design and Synthesis of Some New Quinoline-thiazolidine-2,4-dione-isoxazole Conjugates as EGFR Targeting Agents

Abstract

A series of new quinoline-thiazolidine-2,4-dione-isoxazole conjugates was synthesized and evaluated for in vitro anticancer potency against two breast cancer cell lines, such as MCF-7, MDA-MB231, and the normal cancer cell line MCF-10 A (breast cell line) using erlotinib as a standard drug. (Z)-3-{[5-(4-Methoxyphenyl)isoxazol-3-yl]methyl}-5-(quinolin-4-ylmethylene)thiazolidine-2,4-dione and (Z)-3-{[5-(3,5-dimethoxyphenyl)isoxazol-3-yl]methyl}-5-(quinolin-4-ylmethylene)thiazolidine-2,4-dione showed higher anticancer activities against two cancer cell lines, with IC₅₀ ranging from 3.10 ± 0.43, 2.01 ± 0.03, 3.04 ± 0.05, and 2.00 ± 0.07 μM. Furthermore, (Z)-3-{[5-(4-methoxyphenyl)isoxazol-3-yl]methyl}-5-(quinolin-4-ylmethylene)thiazolidine-2,4-dione, and (Z)-3-{[5-(3,5-dimethoxyphenyl)isoxazol-3-yl]methyl}-5-(quinolin-4-ylmethylene)thiazolidine-2,4-dione displayed more inhibitory activity over tyrosine kinase EGFR when compared with the standard erlotinib.