Abstract
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.