Hai Shang , Jing Guo , Pengtao Wang , Lingyu Li , Yu Tian , Xiaoxue Li , Zhongmei Zou
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引用次数: 10
Abstract
To discover novel anti-inflammatory agents, a series of nitrogen-containing derivatives of aloe-emodin were designed and synthesized. The anti-inflammatory activities of all synthesized derivatives were screened by evaluating their inhibitory effects on LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was determined. Among them, 2i exhibited the best nitric oxide inhibitory activity (IC50 = 3.15 μM), with no obvious toxicity. Further evaluation of the inhibitory effect of 2i on inflammatory cytokines showed that 2i significantly reduced the levels of TNF-α, IL-1β, IL-6 and PGE2. In addition, 2i markedly downregulated the expression levels of iNOS and COX-2. Preliminary mechanistic studies indicated that the anti-inflammatory effect of 2i might be related to the inhibition of the Akt, NF-κB and JNK signaling pathways. Overall, our findings suggested that 2i might be a promising anti-inflammatory agent, or might serve as a new lead compound for the further development of anti-inflammatory agents.
期刊介绍:
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.