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Letters in Drug Design & Discovery
ISSN (Print): 1570-1808
ISSN (Online): 1875-628X
Epub Full Text Article
DOI: 10.2174/15701808113109990042      Price:  $95

Synthesis and Biological Evaluation of New Tubulin Inhibitors: Shikonin Thio-glycoside Derivatives

Author(s): Xiao-Ming Wang, Hong-Yan Lin, Jin-Liang Qi, Li-Fei Bai and Yong-Hua Yang
A novel series of per-O-acetyl-β-D-thoi-glycoside modified shikonin derivatives were designed and synthesized and their anti-proliferative activities were evaluated in vitro on three cancer cell lines. The half maximal inhibitory concentration (IC50) of the mono-, di- and tri- substituted shikonin derivatives vary from 1.58±0.17μg mL-1 to 16.72 ± 1.66μg mL-1. Notably, compared with the parent drug shikonin (IC50 = 2.12 ± 0.17μg mL-1, 6.80 ± 0.21μg mL-1, 5.18 ± 0.69μg mL-1 against MG63, MCF-7 and B16-F10, respectively), IIb (IC50 = 1.04 ± 0.22μg mL-1, 2.02 ± 0.16μg mL-1 and 3.86 ± 0.24μg mL-1) displayed much stronger anti-proliferative effect among them. In addition, IIb exhibited the most potent anti-tubulin activity (IC50 of 3.98 ± 0.43μg mL-1), which compared with shikonin (IC50 = 4.86 ± 0.12μg mL-1). Docking simulation was performed for the position of IIb into the tubulin active site to determine the probable binding model. And the result showed that IIb could bind to the colchicines’ binding site of tubulin nicely. Thus IIb is expected to be the candidate of anti-cancer agent.
Formamide derivatives, synthesis, immunosuppressive bioactivity
State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing 210093 P. R. China.