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Curcumin Recognizes a Unique Binding Site of Tubulin

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Title Curcumin Recognizes a Unique Binding Site of Tubulin
 
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
 
Subject NF-KAPPA-B
MITOCHONDRIAL PATHWAY
APOPTOSIS
CELLS
MICROTUBULES
COLCHICINE
AGENTS
ASSOCIATION
INHIBITION
ACTIVATION
 
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.
 
Publisher AMER CHEMICAL SOC
 
Date 2012-06-26T08:55:44Z
2012-06-26T08:55:44Z
2011
 
Type Article
 
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
 
Language English