苯并咪唑类化合物靶向抗肿瘤作用及其机制研究进展

Advances of benzimidazole derivatives on the function of antitumors and the mechanism

苯并咪唑由于其优秀的杂环系统在生物医学方面发挥着重要的作用。国内外很多研究者以苯并咪唑为母核合成了许多具有良好生物活性的苯并咪唑类衍生物。通过收集近年来国内外关于合成具有靶向抗肿瘤活性的苯并咪唑类衍生物的文献,对其主要抗肿瘤作用靶点如拓扑异构酶、PARP、微管蛋白、G-四链体DNA以及CK2蛋白激酶进行分类介绍,并对不同作用靶点下的苯并咪唑类衍生物进行构效分析,阐述不同基团的引入对该化合物抗肿瘤活性的影响,如甲基的引入增强化合物的亲脂性从而更好地进入细胞产生更好的抗肿瘤活性,吸电子基团F和Cl的引入增强化合物对细胞的毒性等。旨在为合成新型低毒的苯并咪唑类抗肿瘤药物提供理论基础。

Benzimidazole plays an important role in biomedicine because of its excellent heterocyclic system.Many researchers all over the world have synthesized many substituted benzimidazoles with multiple biological activities.In this paper,we collected the literatures on the synthesis of benzimidazole derivatives with antitumor activity in recent years.The main anti-tumor targets such as topoisomerase,PARP,tubulin,G-quadruplex DNA and CK2 protein kinase were introduced.Additionally,the structure-activity relationship of benzimidazole derivatives under different targets was carried out.For example,the methyl substituent at benzimidazole ring increased lipophilicity of the studied compounds and enhanced ability of those compounds to intracellular penetration bringing about higher antitumor.Electron withdrawing groups(F,Cl)on the phenyl ring also enhanced antitumor effect.Our aim is to provide a theoretical basis for the synthesis of novel low toxicity benzimidazole antitumor drugs.