Curcumin Recognizes a Unique Binding Site of Tubulin
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Title |
Curcumin Recognizes a Unique Binding Site of Tubulin
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Creator |
CHAKRABORTI, S
DAS, L KAPOOR, N DAS, A DWIVEDI, V PODDAR, A CHAKRABORTI, G JANIK, M BASU, G PANDA, D CHAKRABARTI, P SUROLIA, A BHATTACHARYYA, B |
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Subject |
NF-KAPPA-B
MITOCHONDRIAL PATHWAY APOPTOSIS CELLS MICROTUBULES COLCHICINE AGENTS ASSOCIATION INHIBITION ACTIVATION |
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Description |
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.
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Publisher |
AMER CHEMICAL SOC
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Date |
2012-06-26T08:55:44Z
2012-06-26T08:55:44Z 2011 |
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Type |
Article
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Identifier |
JOURNAL OF MEDICINAL CHEMISTRY,54(18)6183-6196
0022-2623 http://dx.doi.org/10.1021/jm2004046 http://dspace.library.iitb.ac.in/jspui/handle/100/14236 |
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Language |
English
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