Discovery and Evaluation of Novel Anti-inflammatory Derivatives of Natural Bioactive Curcumin

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2014 Nov 15

PMID 25395833

Citations 12

Authors

Yali Zhang

Xin Jiang

Kesong Peng

Chengwei Chen

Lili Fu

Zhe Wang

Jianpeng Feng

Zhiguo Liu

Huajie Zhang

Guang Liang

Zheer Pan

Affiliations

Soon will be listed here.

Abstract

Curcumin is a natural active product that has various pharmacological activities such as anti-inflammatory effects. Here, we report the synthesis and evaluation of 34 monocarbonyl curcumin analogs as novel anti-inflammatory agents. Among the analogs, the symmetrical heterocyclic type displayed the strongest inhibition of lipopolysaccharide (LPS)-stimulated expression of pro-inflammatory cytokines in macrophages. Analogs S1-S5 and AS29 reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production in a dose-dependent manner and also displayed excellent stability and low cytotoxicity in vitro. In addition, analog S1 dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, analogs S1 and S4 displayed a significant protective effect on LPS-induced septic death in mouse models, with 40% and 50% survival rates, respectively. These data demonstrate that the heterocyclic monocarbonyl curcumin analogs have potential therapeutic effects in acute inflammatory diseases.

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