Abstract
To develop potent anticancer agents, a series of novel 1,3,4-thiadiazoldiazenylacrylonitrile derivatives 2-16 were designed and synthesized using (1,3,4-thiadiazol-2-yl) carbonohydrazonoyl dicyanide (2) as starting material. The radical scavenging activity of the synthesized compounds was evaluated, and it was observed that the compounds have radical scavenging properties. For studying the radical scavenging activity of the synthesized compounds, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method was applied. It was found that compounds 12-16 are the most potent antioxidant compounds compared to the results of ascorbic acid (reference drug). Cytotoxicity studies of the newly synthesized compounds were performed against two mammalian cancer cell lines, HepG2, and MCF-7 cells. Compound 15 showed an IC
50
value (11.5 ± 0.6 µM) that is very similar to DOX as a standard for the two used cell lines. The most promising values were observed from compounds 5 and 12-16 (very strong activity). Histopathology of liver tissues treated with compound 15 confirmed its anticancer activity. Molecular docking (MD) simulations were run to evaluate the putative binding ability of the most promising anti-cancer synthesized compounds 5 and 12-16 with the human cyclin-dependent kinase 2 (CDK2). Based on MD results as well as physicochemical and pharmacokinetic (ADMET) predictions, the compounds under investigation are promising candidates for the future development of novel anticancer agents targeting CDK2.