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.
