Design, synthesis and anti-inflammatory evaluation of aloe-emodin derivatives as potential modulators of Akt, NF- κB and JNK signaling pathways

Eur J Med Chem. 2022 Jun 2;238:114511. doi: 10.1016/j.ejmech.2022.114511. Online ahead of print.ABSTRACTTo 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.PMID:35689856 | DOI:10.1016/j.ejmech.2022.114511
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research
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