New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and study.

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione , 1,3,4-thiadiazole aryl urea and cyanothiouracil moieties was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds and proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds and inhibited cell population in the S phase, whereas inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.