Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety.

Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2 H )-yl)-3-phenylthiourea ( 2 ) was prepared and reacted with various hydrazonoyl halides 3a - h, α-haloketones 5a - d , 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b , which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a - h, 3-phenyl-4-arylthiazoles 6a - d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b , respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC 50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC 50 = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.