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A new class of compounds, which include s -triazine with pyrimidinetrione or thiopyrimidinedione moiety through a hydrazone linkage, were synthesized and characterized. The newly synthesized s -triazine hydrazone derivatives were evaluated in vitro against four cancer cell lines: A549, HepG2, HCT-116, and MCF-7. Several derivatives showed growth inhibition activity in the low microgram range. The results reveal that the barbiturate derivatives showed poor to no activity, while thiobarbiturate derivatives showed better activity than the analogues barbiturate derivatives. The substituents on the s-triazine moiety have a great effect on the antiproliferative activity, where derivatives with the piperidino and diethylamino on the s -triazine ring ( 5h ) showed the highest activity against all of the tested cell lines (IC 50 1.6 ± 0.6, 3.8 ± 0.3, 1.9 ± 0.4, and 1.2± 0.5 μg/mL for the tested cell lines A549, HepG2, HCT-116, and MCF-7, respectively). These results indicate that thiobarbiturates- s -triazine hydrazone derivatives may provide an excellent scaffold for the development of an anticancer drug candidate.

Barbiturate- and Thiobarbituarte-Based s-Triazine Hydrazone Derivatives with Promising Antiproliferative Activities