Curcumin Recognizes a Unique Binding Site of Tubulin

被引：104

作者：

Chakraborti, Soumyananda ^{[1
]}

Das, Lalita ^{[1
]}

Kapoor, Neha ^{[6
]}

Das, Amlan ^{[2
]}

Dwivedi, Vishnu ^{[6
]}

Poddar, Asim ^{[1
]}

Chakraborti, Gopal ^{[2
]}

Janik, Mark ^{[3
]}

Basu, Gautam ^{[4
]}

Panda, Dulal ^{[5
]}

Chakrabarti, Pinak ^{[1
]}

Surolia, Avadhesha ^{[6
]}

Bhattacharyya, Bhabatarak ^{[1
]}

机构：

[1] Bose Inst, Dept Biochem, Kolkata 700054, India

[2] Univ Calcutta, Dr BC Guha Ctr Genet Engn & Biotechnol, Kolkata 700019, India

[3] SUNY Coll Fredonia, Dept Chem, Fredonia, NY 14063 USA

[4] Bose Inst, Dept Biophys, Kolkata 700054, India

[5] Indian Inst Technol, Dept Biosci & Bioengn, Bombay 400076, Maharashtra, India

[6] Natl Inst Immunol, Ctr Mol Med, New Delhi 110012, India

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 18期

关键词：

NF-KAPPA-B; APOPTOSIS; MICROTUBULES; COLCHICINE; ASSOCIATION; INHIBITION; ACTIVATION; INSIGHT; ANALOGS; COMPLEX;

D O I：

10.1021/jm2004046

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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 angstrom away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure-activity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.

引用

页码：6183 / 6196

页数：14

共 44 条

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