A series of bis(benzo[g]indoles) bridged by CX‐(CH2)nN(Me)(CH2)n‐CX (X = O, S, H2; n = 2,3) was synthesized as bifunctional antitumor agents and evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. The parent compounds 2a,b exhibited a good level of activity and derivates 2c— g,i,k demonstrated significant inhibitory effects, all with IC50 values in the low micromolar range. The thioamide analogue 2j showed less potency. It is interesting to note that introduction of substituents on the benzene ring of the benzo[g]indole portion of 2a,b did not affect activity, with the only exception of the 7,8‐dichloro derivative 2h which became less potent. One member of this series, 2i, was then tested in the hollow fiber cell assay to evaluate, in a preliminary fashion, its in vivo antineoplastic activity. Molecular modelling studies were performed on amide 2a and thioamide 2j to explain the loss of activity of 2j as to 2a. Finally, compound 2a behaved as a typical DNAintercalating agent, as judged from viscosity measurements with Poly(dA‐dT) .. poly(dA‐dT).

中文翻译：

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双(苯并[g]吲哚-3-甲酰胺)和相关化合物的合成和细胞毒性

合成了一系列由 CX-(CH2)nN(Me)(CH2)n-CX (X = O, S, H2; n = 2,3) 桥接的双(苯并[g]吲哚)作为双功能抗肿瘤剂和由美国国家癌症研究所评估对多种人类癌细胞系的细胞毒活性。母体化合物 2a,b 表现出良好的活性水平，衍生物 2c-g,i,k 表现出显着的抑制作用，IC50 值均在低微摩尔范围内。硫代酰胺类似物 2j 的效力较低。有趣的是，在 2a,b 的苯并 [g] 吲哚部分的苯环上引入取代基不会影响活性，唯一的例外是 7,8-二氯衍生物 2h 变得不那么有效。然后在中空纤维细胞试验中测试了该系列的一个成员 2i，以初步评估其体内抗肿瘤活性。对酰胺 2a 和硫代酰胺 2j 进行了分子建模研究，以解释 2j 对 2a 的活性丧失。最后，根据使用 Poly(dA-dT) .. poly(dA-dT) 的粘度测量判断，化合物 2a 表现为典型的 DNA 嵌入剂。