1-甲基-2-喹诺酮类衍生物的合成及其抗肿瘤活性

以喹啉类化合物为原料，经甲基化反应和氧化反应制得中间产物2-喹诺酮类化合物(2a~2c)； 2a~2c经硝化反应制得7个硝化-2-喹诺酮类化合物{3a~3g)； 3a, 3e~3g经移位取代反应合成了4个1-甲基化-4-氰化-2-喹诺酮类衍生物(4a, 4e~4g)，其结构经¹H NMR， ¹³C NMR和HR-MS(EI)确证。采用MTT法评价了化合物对MCF-7, H1299, A549, PC-12, CT-26及HepG-2肿瘤细胞的抗增殖作用。研究结果表明：部分化合物对肿瘤细胞的抑制活性明显高于喹啉系列物，其中1,8-二甲基-3,5,7-三硝基-2-喹诺酮(3e)显著抑制六种肿瘤细胞的增殖，对A549的抑制活性最高，IC₅₀为2.05 μmol·L^-1； 1-甲基-6,8-二硝基-4-氰基-2-喹诺酮(4a)可选择性抑制A549和CT-26肿瘤细胞，IC₅₀分别为9.34 μmol·L^-1和18.43 μmol·L^-1。

Synthesis and Antitumor Activities of 1-Methy-2-quinolone Derivatives

Three 2-quinolones (2a ~2c) were synthesized by methylation and oxidation under basic condition from quinolines.Seven nitro-2-quinolones(3a~3g) were obtained by nitration of 2a~2c. Finally, four 1-methyl-4-cyanide-2-quinolones(4a, 4e~4g) were synthesized by cine-substitution reac-tion of 3a, 3e~3g with potassuim cyanide .The structures were confirmed by 1 H NMR, 13 C NMR and HR-MS( EI) .The antitumor activities of the compounds were investigated by MTT assay against MCF -7, H1299, A549, PC-12, CT-26 and HepG-2.The results showed that some of compounds exhibited better inhibition activities than quinolines .1,8-Dimethyl-3,5,7-trinitroquinolin-2 (1H)-one (3e) exhibited good inhibition activities against the six cancer cell lines , especially A549 cell with IC50 of 2.05μmol· L-1 .1-Methyl-6,8-dinitro-2-oxo-1,2-dihydroquinoline-4-carbonitrile (4a) showed better inhibition activ-ities against A549 and CT-26 with IC50 of 9.34μmol· L-1 and 18.43μmol· L-1 , respectively .