New thiazole derivative as a potential anticancer and topoisomerase II inhibitor.

To shed light on the significance of thiazole derivatives in the advancement of cancer medication and to contribute to therapeutic innovation, we have designed the synthesis and antiproliferative activity investigation of 5-(1,3-dioxoisoindolin-2-yl)-7-(4-nitrophenyl)-2-thioxo-3,7-dihydro-2H-pyrano[2,3-d] thiazole-6-carbonitrile, the structure of thiazole derivative was confirmed by spectroscopic techniques UV, IR and NMR. The cytotoxic activity (in vitro) of the new hybrid synthesized compound on five human cancer cell lines; human liver hepatocellular carcinoma (HepG-2), colorectal carcinoma (HCT-116), breast adenocarcinoma (MCF-7), and epithelioid carcinoma (Hela), and a normal human lung fibroblast (WI-38) was studied using MTT assay. The compound exhibited a strong cytotoxicity effect against HepG-2 and MCF-7. The interaction of the newly synthesized compound with calf-thymus DNA (CT-DNA) was investigated at pH 7.2 by using UV-Vis absorption measurements, also, molecular docking was carried out to investigate the DNA binding affinity of the proposed compound with the prospective target, DNA (PDB ID: 1d12). Finally, molecular docking was carried out to examine the binding patterns with the prospective target, DNA-Topo II complex (PDB-code: 3QX3). Results indicated that the investigated compound strongly binds to CT-DNA via intercalative mode, and correlated with those obtained from molecular docking and in agreement with that of in vitro cytotoxicity activity.