{"title":"针对nf - κ b的类黄酮衍生物的细胞毒性和抗炎活性。","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":"{\"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. 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引用次数: 7
摘要
核因子- kappab (NF-kappaB)已被报道调控与癌症和炎症有关的各种基因。因此,抑制NF-kappaB的药物可能同时具有抗炎和抗癌特性。因此,有必要发现新的化合物,不仅要有潜在的铅,而且要毒性更小,成本更低。目的研究以NF-kappaB为靶点,开发新的合成抗炎和细胞毒药物。方法采用紫外、红外、1H-NMR、13C-NMR、质谱等方法对化合物进行表征。采用MTT法测定合成化合物对多种癌细胞的体外细胞毒性和卡拉胶诱导足跖水肿模型的体内抗炎作用。选定的化合物用碘化丙啶进行细胞周期分析。使用Auto Dock 4.2对NF-kappaB活性位点进行对接研究。结果合成了三个系列的化合物,并用各种光谱技术对其进行了表征。测试化合物(10b)、(1c)和(2c)被发现是最有效的抗炎剂,而化合物如(10b)、(6b)、(4b)、(2b)、(6a)、(4a)、(5c)和(3c)在不同的癌细胞系中显示出有希望的细胞毒性,随后对选定的化合物((10b)和(4b)进行细胞周期分析。配体的结合自由能在-6.47 ~ -12.50之间。千卡/摩尔。结论化合物(10b)具有较强的抗炎和细胞毒作用。计算机方法与湿式实验室实验是一致的。有希望的化合物已显示出诱导细胞周期阻滞在G2/M期。
Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB.
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.