蒎烷基噻唑腙类衍生物的合成及抗肿瘤活性研究

Synthesis and Antitumor Activity of Pinanyl Thiazole?Hydrazone Derivatives

摘要:

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~n[请不要用加粗，请改正，下同。][已修改]，采用FTIR，1HNMR，13CNMR和HRMS等分析手段对化合物的结构进行了表征。考察了化合物4a~n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HepG2、8226、A549和231细胞的IC50分别低至5.8、8.8、7.1和10.6 μmol/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9.7 μmol/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40 μmol/L时，A549细胞的总凋亡率从6.5%增加到47.2%，G2/M期的细胞数量从13.5%上升至51.7%。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[G2/M期细胞数量从多少变为多少？请给出数据。][已给出]。

Abstract:

Pinanyl thiazole hydrazone derivatives 4a~n were synthesized from nopinone via addition, condensation and cyclization, and their structures were characterized by FTIR, 1HNMR, 13CNMR and HRMS. The antitumor activities of compounds 4a~n against four human cancer cell lines including HepG2, RPMI-8226, A549 and MDA-MB-231 were evaluated in vitro. The test results showed that compounds 4a had best antitumor activity against the above four cancer cell, IC50 values for HepG2, RPMI-8226, A549 and MDA-MB-231 as low as 5.8, 8.8, 7.1 and 10.6 μmol/L, respectively; compound 4c also had stronger activity and the IC50 values was 8.9, 8.7, 7.3 and 9.7 μmol/L, respectively. Cell apoptosis and cell cycle experiments results indicated that as the concentrations of compound 4a increased from 0 to 40 μmol/L, the total apoptotic rate of A549 cells increased from 6.5% to 47.2%, and the number of cells in G2/M phase increased from 13.5% to 51.7%. The above results indicated that compound 4a effectively fuelled A549 cells apoptosis in a dose-dependent manner and arrested the cell cycle at the G2/M phase.