Synthesis, antitumor evaluation and molecular docking study of a novel podophyllotoxin-lonidamine hybrid

Abstract

A novel podophyllotoxin-lonidamine hybrid was synthesized, and evaluated for its in vitro cytotoxicity by CCK-8 assay. The conjugate, Da, exhibited comparable antiproliferative activity in human normal and multidrug-resistance leukemia cancer cells. Flow cytometry suggested that Da could induce G2 phase cycle arrest and apoptosis of resistant K562/VCR cells, simultaneously increase the mitochondrial membrane depolarization. Furthermore, immunocytochemistry showed that Da could significantly disrupt the microtubule organization in K562/VCR cells. Molecular modeling demonstrated that Da was able to bind into the colchicine site of tubulin.