Al Rasheed Hessa, Dahlous Kholood, Sharma Anamika, Sholkamy Essam, El-Faham Ayman, de la Torre Beatriz G, Albericio Fernando
Department of Chemistry, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4000, South Africa.
ACS Omega. 2020 Jun 23;5(26):15805-15811. doi: 10.1021/acsomega.0c00468. eCollection 2020 Jul 7.
A new class of compounds, which include -triazine with pyrimidinetrione or thiopyrimidinedione moiety through a hydrazone linkage, were synthesized and characterized. The newly synthesized -triazine hydrazone derivatives were evaluated 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 -triazine ring () showed the highest activity against all of the tested cell lines (IC 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--triazine hydrazone derivatives may provide an excellent scaffold for the development of an anticancer drug candidate.
合成并表征了一类新的化合物，这类化合物包括通过腙键连接嘧啶三酮或硫代嘧啶二酮部分的三嗪。对新合成的三嗪腙衍生物针对四种癌细胞系（A549、HepG2、HCT - 116和MCF - 7）进行了评估。几种衍生物在低微摩尔范围内显示出生长抑制活性。结果表明，巴比妥酸盐衍生物显示出较差或无活性，而硫代巴比妥酸盐衍生物显示出比类似的巴比妥酸盐衍生物更好的活性。三嗪部分上的取代基对抗增殖活性有很大影响，其中在三嗪环上带有哌啶基和二乙氨基的衍生物（）对所有测试细胞系显示出最高活性（对于测试细胞系A549、HepG2、HCT - 116和MCF - 7，IC分别为1.6±0.6、3.8±0.3、1.9±0.4和1.2±0.5μg/mL）。这些结果表明硫代巴比妥酸盐 - 三嗪腙衍生物可能为开发抗癌候选药物提供一个优良的骨架。
