A Potent Anticancer Agent of Shikonin Derivative Targeting Tubulin

In this study, a shikonin ester derivative, compound 3g, was selected to evaluate its anticancer activities and we found that compound 3g exhibited better antitubulin activities against the human HepG2 cell line with an IC50 value of 1.097 μM. Furthermore, the inhibition of tubulin polymerization results indicated that compound 3g demonstrated the most potent antitubulin activity (IC50 = 13.88), which was compared with shikonin and colchicine as positive controls (IC50 = 25.28 μM and 22.56 μM), respectively. Compound 3g was simulated to have good binding site with tubulin and arrested the cell cycle at G2/M phase, which also induces apoptosis in HepG2 cells, in which P53 and members of Bcl-2 protein family were both involved in the progress of apoptosis revealed by western blot. Confocal microscopy observations revealed compound 3g targeted tubulin and altered its polymerization by interfering with microtubule organization. Based on these results, compound 3g functions as a potent anticancer agent targeting tubulin. Chirality 27:274–280, 2015.. © 2015 Wiley Periodicals, Inc.