Synthesis, biological evaluation of novel thiopyrano[2,3-d]thiazoles incorporating arylsulfonate moiety as potential inhibitors of tubulin polymerization, and molecular modeling studies

Abstract

Novel series of thiopyrano[2,3-d]1,3-thiazole derivatives incorporating arylsulfonate moiety were synthesized and characterized by 1H NMR, 13C NMR, MS, and IR. The synthesized compounds 6a–d, 8a–t, 10a–f, and 11a,b were evaluated for the cytotoxicity activity against four human cancer cell lines concerning mammary gland (MCF7), epithelioid carcinoma (Hela), human prostate cancer (PC3), and Hepatocellular carcinoma (HepG2). Compound 8d showed higher anticancer activity against MCF7 cell line (IC50 = 3.90 ± 0.4 µM) compared to the standard drug doxorubicin (IC50 = 4.17 ± 0.2 µM). Furthermore, compounds 6a has anticancer activity near to the standard drug doxorubicin against MCF7 and Hela cell lines with IC50 = 5.38 ± 0.6 µM, and 7.63 ± 0.8 µM, respectively. On the other hand, compound 8b exhibited an inhibitory effect against tubulin polymerization with an IC50 = 0.832 ± 0.031 µg/ml, which was similar to the positive control Colchicine (IC50 = 0.810 ± 0.10). The arylsulfonate moiety in 2,4-thiazolidinedithione core exerted a key effect on the anticancer activities of target compounds, according to structure-activity relationships (SARs) and docking studies. In HepG2 cells, compound 8b also caused cell cycle arrest at the G2/M phase and induced apoptosis.