Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: <i>in-vitro</i> anticancer evaluation and <i>in-silico</i> studies

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound <b>12a</b> was found to be the most potent candidate against the investigated cell lines with IC₅₀ values of 2, 10, and 40 µM, respectively. Furthermore, the synthesised derivatives were tested <i>in vitro</i> for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an <i>in vitro</i> viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound <b>12a</b> was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound <b>12a</b> against VEGFR-2.