Curcumin Recognizes a Unique Binding Site of Tubulin

Chakraborti, Soumyananda ; Das, Lalita ; Kapoor, Neha ; Das, Amlan ; Dwivedi, Vishnu ; Poddar, Asim ; Chakraborti, Gopal ; Janik, Mark ; Basu, Gautam ; Panda, Dulal ; Chakrabarti, Pinak ; Surolia, Avadhesha ; Bhattacharyya, Bhabatarak (2011) Curcumin Recognizes a Unique Binding Site of Tubulin Journal of Medicinal Chemistry, 54 (18). pp. 6183-6196. ISSN 0022-2623

Full text not available from this repository.

Official URL: http://doi.org/10.1021/jm2004046

Related URL: http://dx.doi.org/10.1021/jm2004046

Abstract

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 Å 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.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society
ID Code:129125
Deposited On:08 Nov 2022 11:01
Last Modified:08 Nov 2022 11:01

Repository Staff Only: item control page