Hai Shang , Jing Guo , Pengtao Wang , Lingyu Li , Yu Tian , Xiaoxue Li , Zhongmei Zou
{"title":"作为Akt、NF-κB和JNK信号通路潜在调节剂的芦荟大黄素衍生物的设计、合成和抗炎评价","authors":"Hai Shang , Jing Guo , Pengtao Wang , Lingyu Li , Yu Tian , Xiaoxue Li , Zhongmei Zou","doi":"10.1016/j.ejmech.2022.114511","DOIUrl":null,"url":null,"abstract":"<div><p><span>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, </span><strong>2i</strong> exhibited the best nitric oxide inhibitory activity (IC<sub>50</sub> = 3.15 μM), with no obvious toxicity. Further evaluation of the inhibitory effect of <strong>2i</strong><span> on inflammatory cytokines showed that </span><strong>2i</strong> significantly reduced the levels of TNF-α, IL-1β, IL-6 and PGE2. In addition, <strong>2i</strong><span> markedly downregulated the expression levels of iNOS and COX-2. Preliminary mechanistic studies indicated that the anti-inflammatory effect of </span><strong>2i</strong><span> might be related to the inhibition of the Akt, NF-κB and JNK signaling pathways. Overall, our findings suggested that </span><strong>2i</strong> might be a promising anti-inflammatory agent, or might serve as a new lead compound for the further development of anti-inflammatory agents.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2022-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"10","resultStr":"{\"title\":\"Design, synthesis and anti-inflammatory evaluation of aloe-emodin derivatives as potential modulators of Akt, NF-κB and JNK signaling pathways\",\"authors\":\"Hai Shang , Jing Guo , Pengtao Wang , Lingyu Li , Yu Tian , Xiaoxue Li , Zhongmei Zou\",\"doi\":\"10.1016/j.ejmech.2022.114511\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>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, </span><strong>2i</strong> exhibited the best nitric oxide inhibitory activity (IC<sub>50</sub> = 3.15 μM), with no obvious toxicity. Further evaluation of the inhibitory effect of <strong>2i</strong><span> on inflammatory cytokines showed that </span><strong>2i</strong> significantly reduced the levels of TNF-α, IL-1β, IL-6 and PGE2. In addition, <strong>2i</strong><span> markedly downregulated the expression levels of iNOS and COX-2. Preliminary mechanistic studies indicated that the anti-inflammatory effect of </span><strong>2i</strong><span> might be related to the inhibition of the Akt, NF-κB and JNK signaling pathways. Overall, our findings suggested that </span><strong>2i</strong> might be a promising anti-inflammatory agent, or might serve as a new lead compound for the further development of anti-inflammatory agents.</p></div>\",\"PeriodicalId\":314,\"journal\":{\"name\":\"European Journal of Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2022-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"10\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0223523422004135\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0223523422004135","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Design, synthesis and anti-inflammatory evaluation of aloe-emodin derivatives as potential modulators of Akt, NF-κB and JNK signaling pathways
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.