Synthesis and Biological Evaluation of Heterocyclic Carboxylic Acyl Shikonin Derivatives. (26th December 2013)

• Record Type: Journal Article
• Authors: Wang, Xiao‐Ming; Lin, Hong‐Yan; Kong, Wen‐Yao; Guo, Jing; Shi, Jing; Huang, Shou‐Cheng; Qi, Jin‐Liang; Yang, Rong‐Wu; Gu, Hong‐Wei; Yang, Yong‐Hua
• Is Part Of: Chemical biology & drug design. Volume 83:Number 3(2014:Mar.)
• Page Start: 334
• Page End: 343
• Publication Date: 2013-12-26
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12247
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12247-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of shikonin derivatives (<bold>1</bold>–<bold>13</bold>) 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 <bold>3</bold> ((<italic>R</italic>)‐1‐(5, 8‐dihydroxy‐1, 4‐dioxo‐1, 4‐dihydronaphthalen‐2‐yl)‐4‐methylpent‐3‐enyl 3‐(1<italic>H</italic>‐indol‐3‐yl)propanoate) and compound <bold>8</bold> ((<italic>R</italic>)‐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 A875 (IC<sub>50</sub> = 0.005 ± 0.001 μ<sc>m</sc>, 0.009 ± 0.002 μ<sc>m</sc>) and HeLa (IC<sub>50</sub> = 11.84 ± 0.64 μ<sc>m</sc>, 4.62 ± 0.31 μ<sc>m</sc>) cancer cell lines <italic>in vitro</italic>, respectively. Shikonin (IC<sub>50</sub> = 0.46 ± 0.002 μ<sc>m</sc>, 4.80 ± 0.48 μ<sc>m</sc>) and colchicine (IC<sub>50</sub> = 0.75 ± 0.05 μ<sc>m</sc>, 17.79 ± 0.76 μ<sc>m</sc>) were used as references. Meanwhile, they also showed the most potent growth inhibitory activity against tubulin (IC<sub>50</sub> of 3.96 ± 0.13 μ<sc>m</sc> and 3.05 ± 0.30 μ<sc>m</sc>, respectively), which were compared with shikonin (IC<sub>50</sub> = 15.20 ± 0.25 μ<sc>m</sc>) and colchicine (IC<sub>50</sub> = 3.50 ± 0.35 μ<sc>m</sc>). Furthermore, from the results of flow cytometer, we found compound <bold>3</bold> can really inhibit HeLa cell proliferation and has low cell toxicity. Based on the preliminary results, compound <bold>3</bold> with potent inhibitory activity in tumor growth may be a potential anticancer agent.</p> </abstract>