Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids

Khan, M. Akram, El-Khatib, Riyad, Rainsford, K. D. and Whitehouse, M. W. (2012) Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids. Bioorganic Chemistry, 40 1: 30-38. doi:10.1016/j.bioorg.2011.11.004


Author Khan, M. Akram
El-Khatib, Riyad
Rainsford, K. D.
Whitehouse, M. W.
Title Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids
Journal name Bioorganic Chemistry   Check publisher's open access policy
ISSN 0045-2068
1090-2120
Publication date 2012-02-01
Sub-type Article (original research)
DOI 10.1016/j.bioorg.2011.11.004
Open Access Status Not Open Access
Volume 40
Issue 1
Start page 30
End page 38
Total pages 9
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Subject 1303 Specialist Studies in Education
1312 Molecular Biology
1605 Policy and Administration
3002 Drug Discovery
Formatted abstract
A variety of novel aromatic and heterocyclic aromatic curcuminoids were synthesised, characterised and their anti-inflammatory activities (AIA) determined in vivo. Some of these compounds also were tested for inflammatory mediator production. The AIA of the main representatives of these compounds were assessed by oral administration to female Wistar rats using (a) acute carrageenan-induced paw oedema, (b) chronic adjuvant arthritis (therapeutic mode), and (c) anti-pyretic activity assessed in the yeast pyrexia. Gastric ulceration was determined in pre-inflamed rats. Natural curcumin showed modest aspirin-like anti-inflammatory activity which was enhanced when co-administered with the PGE1 analogue misoprostol as a synergist. In contrast, four novel curcuminoids (RK-97, RK-103, RK-104 and RK-106) in which the bis-methoxy-phenyl group of curcumin was replaced with bis-dimethoxybutenolidyl- (ascorbate), bis-naphthyl, and bis-furanyl derivatives, respectively, had potent activity in the anti-arthritic assay with little gastric or systemic toxicity, compared with the vehicle-treated controls. Of the curcuminoids the furan RK-106 was the only compound to inhibit production of TNFα and IL-1β in a monocytic cell-line THP-1 in vitro. The inactivity of RK-106 on the production of PGE2 may be related to its absence of gastrotoxicity. None of the curcuminoids exhibited anti-pyretic activity and this may also be related to its insensitivity to PGE2. Thus, these novel curcuminoids, such as RK-106, may warrant the development of new low gastro-toxic anti-inflammatory agents with selective inhibitory activity of cytokine inflammatory mediators.

Highlights
► Organic synthesis of novel curcuminoids including ascorbic acid. ► Spectroscic characterisation of curcuminoids. ► 13C NMR and MS characteristics of curcuminoids. ► In vivo experiments on anti-inflammatory properties of curcuminoids.
Keyword Anti-inflammatory
Curcumin
Curcuminoids
Heterocyclic
Ascorbic acid
In vivo assays
Organic synthesis
Spectroscopy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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