Fuska J, Fusková A, Proksa B
Neoplasma. 1985;32(4):407-14.
The in vitro cytotoxic effects on P388 leukemia cells of 19 derivatives and analogs of 1-benzylidenisoindolin-3-one, 5,6-dihydro-8H-isoquinolo(2,3-a)phthalasin-5-one and 4-benzyl-1,2-dihydrophthalasin-5-one were studied. The derivatives of the first group which preferentially inhibited uridine utilization were more effective. The cytotoxic effects of these substances depended on the quality of substituents, on the presence of a nitrogen atom in the 5-membered heterocycle of the molecule as well as on the spatial arrangement of the molecule. (Z)-narceine imide-N-oxide II and (Z)-3-(6-ethyl-2-methoxy-3,4-methylenedioxy) benzyliden-6,7-dimethoxy-isoindolin-3-one III were the most active agents, both of them causing a decrease in the proliferation rate of P388 cells. After its addition to the culture medium, compound III caused irreversible damages leading to death of the cells. The removal of the inhibitor did not lead to the repair of the damages either. Of the other two groups of substances, 5-hydroxy-3,4,12-trimethoxy-8-methyl-10,11-methylenedioxy-8H-isoquino lo (2,3-a)phthalasin (XVIII) had a marked inhibitory effect which, at concentrations of up to 25 micrograms ml-1, inhibited the proliferation rate of P388 cells.
研究了1-亚苄基异吲哚啉-3-酮、5,6-二氢-8H-异喹啉并(2,3-a)酞嗪-5-酮和4-苄基-1,2-二氢酞嗪-5-酮的19种衍生物和类似物对P388白血病细胞的体外细胞毒性作用。优先抑制尿苷利用的第一组衍生物更有效。这些物质的细胞毒性作用取决于取代基的性质、分子五元杂环中氮原子的存在以及分子的空间排列。(Z)-水仙碱酰亚胺-N-氧化物II和(Z)-3-(6-乙基-2-甲氧基-3,4-亚甲二氧基)亚苄基-6,7-二甲氧基-异吲哚啉-3-酮III是最具活性的药物，它们都导致P388细胞增殖率下降。将化合物III添加到培养基中后，会造成不可逆损伤，导致细胞死亡。去除抑制剂也不会使损伤得到修复。在其他两组物质中，5-羟基-3,4,12-三甲氧基-8-甲基-10,11-亚甲二氧基-8H-异喹啉并(2,3-a)酞嗪(XVIII)具有显著的抑制作用，在浓度高达25微克/毫升时，可抑制P388细胞的增殖率。
