以茚［1,2-b］喹喔啉-11-酮肟、二卤代烷和哌啶或吡咯、吗啉、二丁胺为原料,合成了10种新型茚［1,2-b］喹喔啉-11-酮肟醚(4A-4J),并以HeLa、A549和MCF-7细胞株为模型,采用MTT法评价了其体外细胞毒性. 结果表明:4A、4B、4E、4F和4J对3种细胞株的毒性均高于顺铂;其中,4A、4B和4F的细胞毒性比顺铂高2~6倍.肟醚链长度和末端基团对其细胞毒性有较大的影响. 随肟醚链长度的增大,细胞毒性降低;末端基团为吡咯时细胞毒性较高. 细胞周期、凋亡实验表明4A引起G0/G1和G2/M期阻滞,导致肿瘤细胞凋亡. 说明吡咯修饰的茚［1,2-b］喹喔啉-11-酮肟醚是有潜力的抗肿瘤先导化合物.
Ten novel indeno［1,2-b］quinoxalin-11-one oxime ethers(4A-4J)were synthesized by indeno［1,2-b］quinoxalin-11-one oxime, saturated dihalide, and piperidine or pyrrole, morpholine, and dibutylamine. Their cytotoxicity against HeLa, A549 and MCF-7 cell lines was evaluated by MTT assay. The results indicated that compounds 4A,4B,4E,4F, and 4J showed higher cytotoxicty than cisplatin against HeLa, A549, and MCF-7 cell lines. Among them, 4A, 4B and 4F exhibited 2 to 6 folds higher cytotoxicty than cisplatin. Both the length of oxime ether chain and the nature of the terminal group have important effects on the cytotoxicity. The cell cycle and apoptosis assays indicated that 4A could change the cells cycle ratio, and induce apoptosis. Our results suggest that indeno［1,2-b］quinoxalin-11-one oxime ether modified by pyrrole is a potential anti tumor precursor compound.
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