Bisdemethylcurcumin and Structurally Related Hispolon Analogues of Curcumin Exhibit Enhanced Prooxidant, Anti-proliferative and Anti-inflammatory Activities in Vitro

Overview

Journal Biochem Pharmacol

Specialties Biochemistry
Pharmacology

Date 2010 Feb 9

PMID 20138025

Citations 27

Authors

Jayaraj Ravindran

Gottumukkala V Subbaraju

Modukuri V Ramani

Bokyung Sung

Bharat B Aggarwal

Affiliations

Soon will be listed here.

Abstract

Curcumin, a component of turmeric (Curcuma longa), exhibits anti-inflammatory and anti-proliferative activities through the generation of reactive oxygen species (ROS). Curcumin (diferuloylmethane) contains two hydroxyl, two methoxy and two phenyl groups but how these groups contribute to its activity is poorly understood. We synthesized analogues that varied in inclusion of these groups and compared their activity. We found that bisdemethylcurcumin (BDC) was more potent than curcumin as an anti-inflammatory agent as indicated by suppression of TNF-induced NF-kappaB activation, more potent as an anti-proliferative agent, and more potent in inducing ROS. Hispolon, which lacks one aromatic unit in relation to curcumin, also exhibited enhanced anti-inflammatory and anti-proliferative activities. When synthetic curcumin (Cur-S) was compared with bisdemethylcurcumin (BDC), hispolon, hispolon methyl ether (HME), dehydroxy hispolon (DH), hydroxy hispolon (HH), methoxy hispolon methyl ether (MHME), and methoxy hispolon (MH), we found that following order of anti-inflammatory activity: BDC=Hispolon>HME>HH>Cur-S>MHME>MH>DH; for anti-proliferative: Hispolon>BDC>MHME>Cur-S>MH>HME=HH>DH; and for prooxidant: BDC>Cur-S=MHME>HH>MH+HME>DH (254-1414 mean fluorescence intensity). Thus, dehydroxy hispolon was least potent for all three activities. Overall the results indicate that the substitution of a hydroxyl group for a methoxy group at the meta positions of the phenyl rings in curcumin significantly enhanced the anti-inflammatory activity, and the removal of phenyl ring at the 7(th) position of the heptadiene back bone and addition of hydroxyl group significantly increased the anti-proliferative activity of curcumin.

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