吡唑并喹啉酮类GSK-3抑制剂的合成及其细胞毒活性

Syntheses and Cytotoxic Activities of Pyrazolo-Quinolinones GSK-3 Inhibitors

吡唑并喹啉酮是一类具有抗肿瘤、抗氧化等多种生物活性的新型化合物,具有很好的药用前景,然而目前对该类化合物的合成及生物活性报道较少。本文采用三组分“一锅法”合成得到8个吡唑并喹啉酮衍生物(a~h),并对其体外细胞毒活性进行了初步评价。结果发现,化合物对肿瘤细胞株Hela、HCC1806和A549表现出较好的选择性抑制活性,特别是化合物h对A549的抑制作用最强(IC_(50)=1.31μmol/L)。分子对接结果显示,化合物h与靶点蛋白4PTC之间存在较强的结合作用,可作为潜在的糖原合成酶激酶-3(GSK-3)抑制剂进行深入研究。

Pyrazolo-quinolinones is a new class of compounds with anti-tumor,anti-oxidation and other biological activities,which has a good medicinal prospect.However,there are few reports on the syntheses and biological activities of these compounds.In this paper,eight pyrazolo-quinolinones derivatives(a~h)have been prepared by a three-component“one-pot”reaction,and their cytotoxic activities were evaluated.The results showed that the compounds exhibited good selective cytotoxic activity against tumor cell lines(Hela,HCC1806 and A549),especially compound h showed the best inhibitory effect on A549(IC_(50)=1.31μmol/L).In addition,the molecular docking study indicated that compound h had a strong interaction with the target protein 4PTC,which could be considered as potential glycogen synthase kinase-3 inhibitor for further study.