{"title":"巨噬细胞促炎性和抗炎性细胞因子表达水平的研究吲哚吡啶-甲烷类新型消炎药物的研制","authors":"Manikandan Alagumuthu, Vanshika Srivastava, Manisha Shah, Sivakumar Arumugam, Mohandoss Sonaimuthu, Napoleon Ayyakannu Arumugam","doi":"10.2174/1871523019666191226104724","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Macrophages play a serious part in the instigation, upkeep, and resolution of inflammation. They are activated or deactivated during inflammation progression. Activation signals include cytokines (IF-γ, granulocyte-monocyte colonystimulating factor (GM-CSF), and TNF-α), extracellular matrix proteins, and other chemical mediators. Activated macrophages are deactivated by anti-inflammatory cytokines (IL- 10 and TGF-β (transforming growth factor-beta) and cytokine antagonists that are mainly produced by macrophages. Based on this, the present study aimed to develop novel (E)- Benzylidene-indazolpyridin methanones (Cpd-1-10) as effective anti-inflammatory agents by analyzing pro- and anti-inflammatory cytokine levels in macrophages.</p><p><strong>Objectives: </strong>To determine the anti-inflammatory effect of indazolpyridin-methanones by examining pro- and anti-inflammatory interleukin levels in J77A.1 macrophages.</p><p><strong>Methods: </strong>Expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-10 serum levels measured by ELISA method. Anti-cancer and cytotoxicity studies were carried out by MTT assay. COX-2 seems to be associated with cancers and atypical developments in the duodenal tract. So, a competitive ELISA based COX-2 inhibition assay was done. To validate the inhibitory potentials and to get more insight into the interaction of COX-2 with Cpd1-10, molecular docking was performed.</p><p><strong>Results: </strong>Briefly, the COX-2 inhibitory relative activity was found to be in between the range of 80-92% (Diclofenac showed 84%, IC50 0.95 μM).</p><p><strong>Conclusion: </strong>Cytotoxicity effect of the compounds against breast cancer cell lines found excellent and an extended anticancer study ensured that these compounds are also alternative therapeutic agents against breast cancer. Among all the tested cancer cell lines, the anti- cancer effect on breast cancer was exceptional for the most active compounds Cpd5 and Cpd9.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523019666191226104724","citationCount":"2","resultStr":"{\"title\":\"Pro- and Anti-Inflammatory Cytokine Expression Levels in Macrophages; An Approach to Develop Indazolpyridin-Methanones as a Novel Inflammation Medication.\",\"authors\":\"Manikandan Alagumuthu, Vanshika Srivastava, Manisha Shah, Sivakumar Arumugam, Mohandoss Sonaimuthu, Napoleon Ayyakannu Arumugam\",\"doi\":\"10.2174/1871523019666191226104724\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Macrophages play a serious part in the instigation, upkeep, and resolution of inflammation. They are activated or deactivated during inflammation progression. Activation signals include cytokines (IF-γ, granulocyte-monocyte colonystimulating factor (GM-CSF), and TNF-α), extracellular matrix proteins, and other chemical mediators. Activated macrophages are deactivated by anti-inflammatory cytokines (IL- 10 and TGF-β (transforming growth factor-beta) and cytokine antagonists that are mainly produced by macrophages. Based on this, the present study aimed to develop novel (E)- Benzylidene-indazolpyridin methanones (Cpd-1-10) as effective anti-inflammatory agents by analyzing pro- and anti-inflammatory cytokine levels in macrophages.</p><p><strong>Objectives: </strong>To determine the anti-inflammatory effect of indazolpyridin-methanones by examining pro- and anti-inflammatory interleukin levels in J77A.1 macrophages.</p><p><strong>Methods: </strong>Expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-10 serum levels measured by ELISA method. Anti-cancer and cytotoxicity studies were carried out by MTT assay. COX-2 seems to be associated with cancers and atypical developments in the duodenal tract. So, a competitive ELISA based COX-2 inhibition assay was done. To validate the inhibitory potentials and to get more insight into the interaction of COX-2 with Cpd1-10, molecular docking was performed.</p><p><strong>Results: </strong>Briefly, the COX-2 inhibitory relative activity was found to be in between the range of 80-92% (Diclofenac showed 84%, IC50 0.95 μM).</p><p><strong>Conclusion: </strong>Cytotoxicity effect of the compounds against breast cancer cell lines found excellent and an extended anticancer study ensured that these compounds are also alternative therapeutic agents against breast cancer. Among all the tested cancer cell lines, the anti- cancer effect on breast cancer was exceptional for the most active compounds Cpd5 and Cpd9.</p>\",\"PeriodicalId\":35423,\"journal\":{\"name\":\"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2174/1871523019666191226104724\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/1871523019666191226104724\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1871523019666191226104724","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Pro- and Anti-Inflammatory Cytokine Expression Levels in Macrophages; An Approach to Develop Indazolpyridin-Methanones as a Novel Inflammation Medication.
Background: Macrophages play a serious part in the instigation, upkeep, and resolution of inflammation. They are activated or deactivated during inflammation progression. Activation signals include cytokines (IF-γ, granulocyte-monocyte colonystimulating factor (GM-CSF), and TNF-α), extracellular matrix proteins, and other chemical mediators. Activated macrophages are deactivated by anti-inflammatory cytokines (IL- 10 and TGF-β (transforming growth factor-beta) and cytokine antagonists that are mainly produced by macrophages. Based on this, the present study aimed to develop novel (E)- Benzylidene-indazolpyridin methanones (Cpd-1-10) as effective anti-inflammatory agents by analyzing pro- and anti-inflammatory cytokine levels in macrophages.
Objectives: To determine the anti-inflammatory effect of indazolpyridin-methanones by examining pro- and anti-inflammatory interleukin levels in J77A.1 macrophages.
Methods: Expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-10 serum levels measured by ELISA method. Anti-cancer and cytotoxicity studies were carried out by MTT assay. COX-2 seems to be associated with cancers and atypical developments in the duodenal tract. So, a competitive ELISA based COX-2 inhibition assay was done. To validate the inhibitory potentials and to get more insight into the interaction of COX-2 with Cpd1-10, molecular docking was performed.
Results: Briefly, the COX-2 inhibitory relative activity was found to be in between the range of 80-92% (Diclofenac showed 84%, IC50 0.95 μM).
Conclusion: Cytotoxicity effect of the compounds against breast cancer cell lines found excellent and an extended anticancer study ensured that these compounds are also alternative therapeutic agents against breast cancer. Among all the tested cancer cell lines, the anti- cancer effect on breast cancer was exceptional for the most active compounds Cpd5 and Cpd9.
期刊介绍：
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new anti-inflammatory & anti-allergy agents. Publishing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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