School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, 55 Daxuecheng South Road, Shapingba, Chongqing 401331, PR China.
School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, 55 Daxuecheng South Road, Shapingba, Chongqing 401331, PR China.
Eur J Med Chem. 2018 May 10;151:214-225. doi: 10.1016/j.ejmech.2018.02.079. Epub 2018 Mar 17.
A series of novel azacalix[2]arene[2]pyrimidines were synthesized, and evaluated for their antiproliferative activities against A549, MCF7, SH-SY5Y and CNE human cancer cell lines in vitro by using the CCK-8 assay. A number of compounds showed low micromolar antiproliferative activities against MCF7 cell line. Compound 4j, containing a pyrrolidine moiety, exhibited the strongest inhibitory activity with an IC value of 0.58 μM. Furthermore, breast cancer cells were used to explore the inhibition mechanism of these azacalix[2]arene[2]pyrimidines. The results suggested these compounds were involved in inducing cell apoptosis via up-regulation of caspase-3 and caspase-9 protein expression, and the cell cycle was arrested at the S phase. Our reports here represent the first studies on the biological activities of azacalix[2]arene[2]pyrimidines.
合成了一系列新型的氮杂杯[2]芳烃[2]嘧啶，并通过 CCK-8 法在体外评估了它们对 A549、MCF7、SH-SY5Y 和 CNE 人癌细胞系的抗增殖活性。许多化合物对 MCF7 细胞系表现出低微摩尔的抗增殖活性。含有吡咯烷部分的化合物 4j 表现出最强的抑制活性，IC 值为 0.58 μM。此外，还使用乳腺癌细胞来探索这些氮杂杯[2]芳烃[2]嘧啶的抑制机制。结果表明，这些化合物通过上调半胱天冬酶-3 和半胱天冬酶-9 蛋白表达诱导细胞凋亡，并且细胞周期被阻滞在 S 期。我们的报告代表了对氮杂杯[2]芳烃[2]嘧啶生物活性的首次研究。
