Stable and Potent Analogues Derived from the Modification of the Dicarbonyl Moiety of Curcumin

Chakraborti, Soumyananda and Dhar, Gopa and Dwivedi, Vishnu and Das, Amlan and Poddar, Asim and Chakraborti, Gopal and Basu, Gautam and Chakrabarti, Pinak and Surolia, Avadhesha and Bhattacharyya, Bhabatarak (2013) Stable and Potent Analogues Derived from the Modification of the Dicarbonyl Moiety of Curcumin. In: BIOCHEMISTRY, 52 (42). pp. 7449-7460.

PDF Biochemstry_52-42_7449_2013.pdf - Published Version Restricted to Registered users only Download (1MB) | Request a copy

Abstract

Curcumin has shown promising therapeutic utilities for many diseases, including cancer; however, its clinical application is severely limited because of its poor stability under physiological conditions. Here we find that curcumin also loses its activity instantaneously in a reducing environment. Curcumin can exist in solution as a tautomeric mixture of keto and enol forms, and the enol form was found to be responsible for the rapid degradation of the compound. To increase the stability of curcumin, several analogues were synthesized in which the diketone moiety of curcumin was replaced by isoxazole (compound 2) and pyrazole (compound 3) groups. Isoxazole and pyrazole curcumins were found to be extremely stable at physiological pH, in addition to reducing atmosphere, and they can kill cancer cells under serum-depleted condition. Using molecular modeling, we found that both compounds 2 and 3 could dock to the same site of tubulin as the parent molecule, curcumin. Interestingly, compounds 2 and 3 also show better free radical scavenging activity than curcumin. Altogether, these results strongly suggest that compounds 2 and 3 could be good replacements for curcumin in future drug development.

Item Type:	Journal Article
Publication:	BIOCHEMISTRY
Publisher:	AMER CHEMICAL SOC
Additional Information:	copyright for this article belongs to AMER CHEMICAL SOC
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	28 Nov 2013 11:46
Last Modified:	28 Nov 2013 11:46
URI:	http://eprints.iisc.ac.in/id/eprint/47843

Actions (login required)

View Item