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Insights into structures of imidazo oxazines as potent polyketide synthase XIII inhibitors using molecular modeling techniques
Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-03-30 , DOI: 10.1080/10799893.2020.1742740
Shanthakumar B 1 , Kathiravan M K 1, 2
Affiliation  

Abstract Tuberculosis, a major global health concern, and its drug development toward the disease are too devastating to meet the clinical demands. The present work emphasizes a detailed QSAR study using QSARINS which developed descriptors favoring an excellent model equation. The best model equation generated has four variables namely AlogP, ATSc4, mindssC, and MDEC23 with statistical values R2 = 0.7406, LOF = 0.1858, CCCtr = 0.8510, Q2LOO = 0.6569, Q2LMO = 0.6286, CCCcv = 0.8037, R2ext = 0.8600, and CCCext = 0.9252. The developed QSAR model justifies that the key structural fragments highly correlate with activity. Docking the designed compounds with PKS XIII, a novel target catalyzes the formation of mycolic acids and its results distinctly improve expected antitubercular activity showing all probable interactions. Compounds were further screened for ADME analysis and toxicity. Graphical Abstract

中文翻译:

使用分子建模技术洞察作为有效聚酮合酶 XIII 抑制剂的咪唑并恶嗪的结构

摘要 结核病是一个主要的全球健康问题,其针对该疾病的药物开发具有破坏性,无法满足临床需求。目前的工作强调使用 QSARINS 进行详细的 QSAR 研究,该研究开发了有利于优秀模型方程的描述符。生成的最佳模型方程有四个变量,即 AlogP、ATSc4、mindssC 和 MDEC23,其统计值 R2 = 0.7406、LOF = 0.1858、CCCtr = 0.8510、Q2LOO = 0.6569、Q2LMO = 0.6286、CCCext30、CCCext30、CCCext3、70。 = 0.9252。开发的 QSAR 模型证明关键结构片段与活动高度相关。将设计的化合物与 PKS XIII 对接,一个新的目标催化霉菌酸的形成,其结果显着提高了预期的抗结核活性,显示了所有可能的相互作用。进一步筛选化合物的 ADME 分析和毒性。图形概要
更新日期:2020-03-30
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