咪唑啉-2-酮衍生物的合成及其抗肿瘤活性

Synthesis and antitumor activity of arylsubstituted imidazolin-2-one derivatives

目的设计、合成五元环为咪唑啉2酮的CA4的构象限制类似物,以期得到在体内外具有更好活性的化合物。方法取代苯胺与固体光气反应得取代苯异氰酸酯,不经后处理直接与相应的α氨基苯乙酮盐酸盐在甲苯存在下回流反应得到3,4-二取代苯基咪唑啉2酮1甲酰苯胺和3,4-二取代苯基咪唑啉2酮。经MTT法筛选其对PC3,A549,HO8910,Hela,HL60,K562和HL60R瘤株的抗肿瘤活性,并对化合物4y进行了初步的作用机制研究。结果按上法制得36个未见文献报道的化合物,其结构经1HNMR,MS和元素分析确证。结论体外活性测试表明,化合物4y对人白血病具有选择性的抑制作用,其作用机制主要为诱导凋亡。

Aim To design and synthesize new arylsubstituted imidazolin-2-one analogues as antitumor compounds. Methods Arylsubstituted imidazolin-2-ones were prepared by condensation the appropriate ω-amino-acetophenone hydrochloride with arylisocyanate in toluene. The target compounds prepared in this study were tested for cytotoxicity against PC-3, A549, HO-8910, Hela, HL60, K562 and HL60R cancer cell lines, and mechanism of one of the products 4y was further evaluated with its mechanium. Results Thirty-six new compounds were synthesized and confirmed by ^1H NMR, MS and elemental analysis. One of the synthesized products, compound 4y, displayed an encouraging selective activity against HL60 ceils, and it was partlydue to the cell cycle arrest and cell apoptosis. Conclusion Compound 4y is worthy to be intensively studied.