Design, Synthesis and Biological Evaluation of Cinnamic Acyl Shikonin Derivatives. (26th November 2012)

• Record Type: Journal Article
• Authors: Lin, Hong‐Yan; Chen, Wei; Shi, Jing; Kong, Wen‐Yao; Qi, Jin‐Liang; Wang, Xiao‐Ming; Yang, Yong‐Hua
• Is Part Of: Chemical biology & drug design. Volume 81:Number 2(2013:Feb.)
• Page Start: 275
• Page End: 283
• Publication Date: 2012-11-26
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12077
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Inducing apoptosis is an important and promising therapeutic approach to overcome cancer. Here, we described a series of novel synthesized compounds, cinnamic acyl shikonin derivatives (<bold>1b</bold>–<bold>19b</bold>), which were synthesized starting from shikonin and cinnamic acids, which exhibit anticancer activity via inducing apoptosis <italic>in vitro</italic>. Our flow cytometry results showed that compound <bold>8b</bold>((E)‐1‐(5, 8‐dihydroxy‐1, 4‐dioxo‐1, 4‐dihydronaphthalen‐2‐yl)‐4‐methylpent ‐3‐enyl‐3‐(3‐(trifluoromethyl) phenyl)acrylate) (IC₅₀ = 0.69, 0.65, 1.62 μ<sc>m</sc> for human SW872‐s, A875 and A549 cell lines, respectively) exhibited conspicuous anticancer activities and has low cell toxicity <italic>in vitro</italic>. Therefore, we considered that compound <bold>8b</bold> is potentially to be a candidate of anticancer agent. The proliferation inhibitory effect of compound <bold>8b</bold> was associated with its apoptosis‐inducing effect by activating caspase‐3, caspase‐7, caspase‐9, and PARP. When the level of cleaved caspase‐3, cleaved caspase‐7, cleaved caspase‐9, and cleaved PARP are rise, apoptosis of cancer cells will be induced.</p> </abstract>