In this paper novel isoindolines substituted with cyano and amidino benzimidazoles and benzothiazoles were synthesized as new potential anti-cancer agents. The new structures were evaluated for antiproliferative activity, cell cycle changes, cell death, as well as DNA binding and topoisomerase inhibition properties on selected compounds. Results showed that all tested compounds exerted antitumor activity, especially amidinobenzothiazole and amidinobenzimidazole substituted isoindolin-1-ones and benzimidazole substituted 1-iminoisoindoline that showed antiproliferative effect in the submicromolar range. Moreover, the DNA-binding properties of selected compounds were evaluated by biophysical and biochemical approaches including thermal denaturation studies, circular dichroism spectra analyses and topoisomerase I/II inhibition assays and results identified some of them as strong DNA ligands, harboring or not additional topoisomerase II inhibition and able to locate in the nucleus as determined by fluorescence microscopy. In conclusion, we evidenced novel cyano- and amidino-substituted isoindolines coupled with benzimidazoles and benzothiazoles as topoisomerase inhibitors and/or DNA binding compounds with potent antitumor activities.

在本文中，合成了用氰基和a基苯并咪唑和苯并噻唑取代的新型异吲哚啉作为新的潜在抗癌药。对新结构的抗增殖活性，细胞周期变化，细胞死亡以及所选化合物的DNA结合和拓扑异构酶抑制特性进行了评估。结果表明，所有测试的化合物均具有抗肿瘤活性，尤其是a氨基苯并噻唑和a氨基苯并咪唑取代的异吲哚啉-1-酮和苯并咪唑取代的1-亚氨基异吲哚啉在亚微摩尔范围内均具有抗增殖作用。此外，还通过生物物理和生化方法（包括热变性研究，圆二色性光谱分析和拓扑异构酶I / II抑制分析和结果鉴定出其中一些是强DNA配体，具有或不具有额外的拓扑异构酶II抑制作用，并且能够通过荧光显微镜确定其位于细胞核中。总之，我们证明了新颖的氰基和a基取代的异吲哚啉与苯并咪唑和苯并噻唑作为拓扑异构酶抑制剂和/或具有强大抗肿瘤活性的DNA结合化合物。