{"title":"Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB.","authors":"K. Naik, Sivakumar Thangavel, A. Alam","doi":"10.2174/1872213X10666161114231625","DOIUrl":null,"url":null,"abstract":"BACKGROUND Nuclear factor-kappaB (NF-kappaB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs inhibiting NF-kappaB may possess both anti-inflammatory and anticancer properties. So there is a need to discover novel compounds which should not only be a potential lead but also less toxic and cost effective. OBJECTIVES The aim of the study was to develop new synthetic anti-inflammatory and cytotoxic agents targeting NF-kappaB. METHODS Test compounds were synthesized and characterized by UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized compounds were evaluated for in vitro cytotoxicity by MTT assay against various cancer cell lines and in vivo anti-inflammatory in carrageenan-induced paw edema model. Selected compounds were subjected to cell cycle analysis using propidium iodide. Docking study was done into an active site of NF-kappaB using Auto Dock 4.2. RESULT Three series of compounds were synthesized and characterized by various spectroscopic techniques. The test compounds (10b), (1c) and (2c) were found to be the most potent anti-inflammatory agents, whereas compounds such as (10b), (6b), (4b), (2b), (6a), (4a), (5c) and (3c) have shown promising cytotoxicity in different cancer cell lines, followed by cell cycle analysis of selected compounds ((10b) and (4b)). The free energy of binding of ligands was in the range between -6.47 to -12.50.Kcal/ mole. CONCLUSION compound (10b) was found to be the most potent as both anti-inflammatory and cytotoxic agents. In silico approach was in good tune with the wet lab experiments. The promising compounds have shown to induce cell cycle arrest at G2/M Phase.","PeriodicalId":20960,"journal":{"name":"Recent patents on inflammation & allergy drug discovery","volume":"10 2 1","pages":"119-132"},"PeriodicalIF":4.2000,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1872213X10666161114231625","citationCount":"7","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Recent patents on inflammation & allergy drug discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1872213X10666161114231625","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 7
Abstract
BACKGROUND Nuclear factor-kappaB (NF-kappaB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs inhibiting NF-kappaB may possess both anti-inflammatory and anticancer properties. So there is a need to discover novel compounds which should not only be a potential lead but also less toxic and cost effective. OBJECTIVES The aim of the study was to develop new synthetic anti-inflammatory and cytotoxic agents targeting NF-kappaB. METHODS Test compounds were synthesized and characterized by UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized compounds were evaluated for in vitro cytotoxicity by MTT assay against various cancer cell lines and in vivo anti-inflammatory in carrageenan-induced paw edema model. Selected compounds were subjected to cell cycle analysis using propidium iodide. Docking study was done into an active site of NF-kappaB using Auto Dock 4.2. RESULT Three series of compounds were synthesized and characterized by various spectroscopic techniques. The test compounds (10b), (1c) and (2c) were found to be the most potent anti-inflammatory agents, whereas compounds such as (10b), (6b), (4b), (2b), (6a), (4a), (5c) and (3c) have shown promising cytotoxicity in different cancer cell lines, followed by cell cycle analysis of selected compounds ((10b) and (4b)). The free energy of binding of ligands was in the range between -6.47 to -12.50.Kcal/ mole. CONCLUSION compound (10b) was found to be the most potent as both anti-inflammatory and cytotoxic agents. In silico approach was in good tune with the wet lab experiments. The promising compounds have shown to induce cell cycle arrest at G2/M Phase.
期刊介绍:
Recent Patents on Inflammation & Allergy Drug Discovery publishes review articles by experts on recent patents in the field of inflammation and allergy drug discovery e.g. on novel bioactive compounds, analogs and targets. A selection of important and recent patents in the field is also included in the journal. The journal is essential reading for all researchers involved in inflammation and allergy drug design and discovery.