Abstract: Based on the structure of combretastatin A-4 (CA-4), a microtubulin inhibitor, eight novel compounds were designed and synthesized by introducing different substituents into the benzimidazole backbone which substituted B ring of CA-4, and the structures were characterized by NMR and HRMS. Proliferation inhibition of six tumor cells including A549, HepG2, HCT-116, MCF-7, PC-3 and Siha was measured by MTT method.The effect of active compound on cell migration was evaluated by scratch test.Molecular docking technique was applied to investigate the interaction between the most active compound with the tubulin and PI3K kinases respectively.Compound 4e showed prominent inhibition against six strains of tumor cells, especially with the strongest inhibitory effect on Siha cells (IC₅₀ = 12.18 ± 1.17 μmol/L).Moreover, compound 4e could effectively inhibit cell migration, which deserves further study.Molecular docking study showed that the binding energy to the tubulin of compound 4e was stronger than that of CA-4, and the affinity with PI3Ks displayed that the PI3Kδ subtype kinase was the strongest; its binding energy was -37.2 kJ/mol.This study lays a foundation for the development of anti-tumor drug based on PI3K and microtubulin.