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Synthesis and Biological Evaluation of Heterocyclic Carboxylic Acyl Shikonin Derivatives
Author(s) -
Wang XiaoMing,
Lin HongYan,
Kong WenYao,
Guo Jing,
Shi Jing,
Huang ShouCheng,
Qi JinLiang,
Yang RongWu,
Gu HongWei,
Yang YongHua
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12247
Subject(s) - hela , chemistry , stereochemistry , lead compound , thiophene , cell culture , colchicine , in vitro , cell growth , biological activity , biochemistry , biology , organic chemistry , genetics
A series of shikonin derivatives ( 1 – 13 ) that were acylated selectively by various thiophene or indol carboxylic acids at the side chain of shikonin were synthesized, and their biological activities were also evaluated as potential tubulin inhibitors. Among them, compound 3 (( R )‐1‐(5,8‐dihydroxy‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐4‐methylpent‐3‐enyl 3‐(1 H ‐indol‐3‐yl)propanoate) and compound 8 (( R )‐1‐(5,8‐dihydroxy‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐4‐methylpent‐3‐enyl 2‐(thiophen‐3‐yl)acetate) exhibited good antiproliferative activity of A 875 ( IC 50 = 0.005 ± 0.001 μ m , 0.009 ± 0.002 μ m ) and HeLa ( IC 50 = 11.84 ± 0.64 μ m , 4.62 ± 0.31 μ m ) cancer cell lines in vitro , respectively. Shikonin ( IC 50 = 0.46 ± 0.002 μ m , 4.80 ± 0.48 μ m ) and colchicine ( IC 50 = 0.75 ± 0.05 μ m , 17.79 ± 0.76 μ m ) were used as references. Meanwhile, they also showed the most potent growth inhibitory activity against tubulin ( IC 50 of 3.96 ± 0.13 μ m and 3.05 ± 0.30 μ m , respectively), which were compared with shikonin ( IC 50 = 15.20 ± 0.25 μ m ) and colchicine ( IC 50 = 3.50 ± 0.35 μ m ). Furthermore, from the results of flow cytometer, we found compound 3 can really inhibit HeLa cell proliferation and has low cell toxicity. Based on the preliminary results, compound 3 with potent inhibitory activity in tumor growth may be a potential anticancer agent.