Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists

Abstract

Newly designed thiazolidine-2,4-diones <b>3</b>-<b>7a</b>-<b>c</b> were synthesized, and their anticancer activities were screened against three cancer lines. They showed potent activities against HepG2 compared to the other HCT116 and MCF-7 tumor cell lines. Compounds <b>7c</b> and <b>6c</b> were detected as highly effective derivatives against MCF-7 (IC₅₀ = 7.78 and 8.15 µM), HCT116 (IC₅₀ = 5.77 and 7.11 µM) and HepG2 (IC₅₀ = 8.82 and 8.99 µM). The highly effective derivatives <b>6a</b>-<b>c</b> and <b>7a</b>-<b>c</b> were tested against VERO normal cell lines. All derivatives were evaluated for their VEGFR-2 inhibitory actions and demonstrated high to low activities, with IC₅₀ values varying from 0.08 to 0.93 µM. Moreover, derivatives <b>5a</b>-<b>c</b>, <b>6a</b>-<b>c</b> and <b>7a</b>-<b>c</b> were assessed to verify their in vitro binding affinities to PPARγ and insulin-secreting activities. Finally, docking studies were performed to explore their affinities and binding modes toward both VEGFR-2 and PPARγ receptors.