Curcumin Recognizes a Unique Binding Site of Tubulin

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• 作者：Soumyananda Chakraborti ; Lalita Das ; Neha Kapoor ; Amlan Das ; Vishnu Dwivedi ; Asim Poddar ; Gopal Chakraborti ; Mark Janik ; Gautam Basu ; Dulal Panda ; Pinak Chakrabarti ; Avadhesha Surolia ; Bhabatarak Bhattacharyya
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：September 22, 2011
• 年：2011
• 卷：54
• 期：18
• 页码：6183-6196
• 全文大小：1219K
• 年卷期：v.54,no.18(September 22, 2011)
• ISSN：1520-4804

文摘

Although curcumin is known for its anticarcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogues, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: (i) curcumin acts as a bifunctional ligand, (ii) analogues with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, (iii) a benzylidiene derivative, compound 7, is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed compound 7 to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 脜 away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure鈥揳ctivity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.