Liu Fengyu, Qian Xuhong, Cui Jingnan, Xiao Yi, Zhang Rong, Li Gangyue
State Key Laboratory of Fine Chemicals, Dalian University of Technology, China.
Bioorg Med Chem. 2006 Jul 1;14(13):4639-44. doi: 10.1016/j.bmc.2006.02.016. Epub 2006 Mar 3.
8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and derivatives were prepared and evaluated for cytotoxicity against A549 and P388 cell lines. Based on a novel chromophore precursor 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile 1, the very insoluble 1 was converted to more soluble esters 5 and a series of 3-amino derivatives from 5 were obtained by mild S(N)Ar(H) reaction between 5 and various amines. The biological evaluation indicated that methyl esters 5a are the most cytotoxic with IC(50) values of 0.45 and 0.80 microM (against A549 and P388, respectively) among the parent esters 5a-5f, but 3-amino derivatives 4b and 4c of 5f with bromine showed the highest activity (with IC(50) values of 0.019-0.60 microM) among the 3-amino derivatives.
制备了8-氧代-8H-苊并[1,2-b]吡咯-9-羧酸酯及其衍生物，并评估了它们对A549和P388细胞系的细胞毒性。基于新型发色团前体8-氧代-8H-苊并[1,2-b]吡咯-9-腈1，将极难溶解的1转化为更易溶解的酯5，并通过5与各种胺之间的温和S(N)Ar(H)反应从5获得了一系列3-氨基衍生物。生物学评估表明，在母体酯5a - 5f中，甲酯5a的细胞毒性最强，IC(50)值分别为0.45和0.80微摩尔（分别针对A549和P388），但5f的含溴3-氨基衍生物4b和4c在3-氨基衍生物中表现出最高活性（IC(50)值为0.019 - 0.60微摩尔）。
