蒎烷基噻唑腙类衍生物的合成及其抗肿瘤活性

Synthesis and Antitumor Activity of Pinanyl Thiazole Hydrazone Derivatives

以诺蒎酮为原料,经过加成、缩合、环化等反应,合成出蒎烷基噻唑腙衍生物4a～4n,采用FTIR、1HNMR、13CNMR和HRMS对化合物的结构进行了表征。考察了化合物4a～4n对人肝癌细胞(HepG2)、人多发性骨髓瘤细胞(RPMI-8226)、人肺癌细胞(A549)和乳腺癌细胞(MDA-MB-231)的抗肿瘤活性。实验结果表明,化合物4a的抗肿瘤活性最强,其对Hep G2、8226、A549和231细胞的IC50分别低至5.8、8.8、7.1和10.6μmol/L;化合物4c的抗肿瘤活性也较强,其IC50分别为8.9、8.7、7.3和9.7μmol/L。细胞凋亡和周期实验数据显示,当化合物4a浓度从0增加到40μmol/L时,A549细胞的总凋亡率从6.55%增加到47.20%,G2/M期的细胞数量从13.50%上升至51.72%。以上结果表明,化合物4a能够诱导A549细胞凋亡,并将细胞有丝分裂周期阻滞在G2/M期。

Pinanyl thiazole hydrazone derivatives 4 a^4 n were synthesized from nopinone via addition,condensation and cyclization,and their structures were characterized by FTIR,1 HNMR,13 CNMR and HRMS.The antitumor activities of compounds 4 a^4 n against four human cancer cell lines including HepG2,RPMI-8226,A549 and MDA-MB-231 were evaluated in vitro.The results showed that compound 4 a had the best antitumor activity against the above four cancer cell lines,the IC50 values against HepG2,RPMI-8226,A549 and MDA-MB-231 were as low as 5.8,8.8,7.1 and 10.6 μmol/L,respectively.Compound 4 c also had stronger activity with the corresponding IC50 values of 8.9,8.7,7.3 and 9.7 μmol/L.Cell apoptosis and cell cycle experiments indicated that when the concentration of compound 4 a increased from 0 to 40 μmol/L,the total apoptotic rate of A549 cells increased from 6.55% to 47.20%,and the number of cells in G2/M phase increased from 13.50% to 51.72%.It was found that compound 4 a could induce apoptosis in A549 cells in a dose-dependent manner and arrest the cell cycle at the G2/M phase.