首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Antioxidant activity of novel quinazolinones bearing sulfonamide: Potential radiomodulatory effects on liver tissues via NF-kappa B/ PON1 pathway
【24h】

Antioxidant activity of novel quinazolinones bearing sulfonamide: Potential radiomodulatory effects on liver tissues via NF-kappa B/ PON1 pathway

机译:新型喹唑啉酮的抗氧化活性磺胺胺:NF-Kappa B / PON1途径对肝组织的潜在放射性调节作用

获取原文
获取原文并翻译 | 示例
           

摘要

In order to discover new antioxidants, fifteen novel quinazolinone derivatives bearing benzenesulfonamide moiety with variable heterocyclic tail, were synthesized and their structures were established on the basis of spectral data. All the synthesized compounds were screened for their antioxidant potential using DPPH assay in comparison to ascorbic acid. The N-(pyrazin-2-yl)-2-[(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-yl)thio]acetamide 16 was the most active scaffold in this series with greater scavenging activity than that of ascorbic acid. In vivo acute toxicity study of compound 16 indicates its relative safety with a median lethal dose of 200 mg/kg. The possible antioxidant and hepatoprotective activities of compound 16 were evaluated in irradiated mice. Compound 16 caused mitigation of gamma radiation-induced oxidative stress verified by the decline in MDA, ROS and NF-kappa B levels. Moreover, SOD and PON1 activities, as well as Zn2+ levels, were improved in liver tissues. Furthermore, molecular docking of compound 16 inside the active site of SOD and PON1 demonstrated the same binding interactions as that of the co-crystallized ligands considering the binding possibilities and energy scores. These findings support that compound 16 may represent a structural lead for developing new antioxidants and hepatoprotective agents. (C) 2020 Elsevier Masson SAS. All rights reserved.
机译:为了发现新的抗氧化剂,合成了含有可变杂环的十五种新型喹唑啉酮衍生物,其结构是基于光谱数据建立的结构。与抗坏血酸相比,使用DPPH测定筛选所有合成的化合物的抗氧化潜力。 n-(吡嗪-2-基)-2 - [(4-氧代-3-(4-磺酰苯甲酰基)-3,4-二氢喹唑啉-2-基)硫代乙酰胺16是该系列中最活跃的支架比抗坏血酸更大的清除活性。在体内急性毒性研究中的化合物16表明其相对安全性具有200mg / kg的中值致命剂量。在辐照小鼠中评价化合物16的可能抗氧化剂和肝脏保护活性。化合物16引起减轻γ辐射诱导的氧化应激,通过MDA,ROS和NF-Kappa B水平的下降验证。此外,在肝脏组织中改善了SOD和PON1活性以及Zn2 +水平。此外,SOD和PON1的活性位点内的化合物16的分子对接证明了考虑到结合可能性和能量分数的共结晶配体的结合相互作用。这些发现支持该化合物16可以代表用于开发新的抗氧化剂和肝保护剂的结构铅。 (c)2020 Elsevier Masson SAS。版权所有。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号