Scholarlink

<p>The current study has detailed the computational methodologies to assess the therapeutic potential of carbonyl-substituted derivatives <b>1</b>–<b>4</b> of 8-hydroxyquinoline (8-HoQ). Various computational techniques, including density functional theory, global chemical descriptors and molecular docking, were applied to analyze the properties of the 8-HoQ derivatives and the interactions between them and target proteins. Molecular stability and reactivity were evaluated using frontier molecular orbital (FMO) and molecular electrostatic potential studies, while topological visualizations, such as electron localization function, localized orbital locator, reduced density gradient, and interaction region indicator, provided insights into molecular polar charge characteristics. Molecular reactive sites identified from these analyzes were utilized in molecular docking studies targeting Glutamate Kinase (GK), a previously untapped enzyme in tuberculosis treatment. The 8-HoQ derivatives <b>1</b>–<b>4</b> exhibited binding affinity of -6.8, -7.5, -7.2, and − 8.2&#xa0;kcal mol⁻¹, respectively, which are higher than the standard ligand of L-Glutamic acid, demonstrating their potential as GK activators to inhibit <i>Mycobacterium tuberculosis</i> (mtb). The high binding score derivative 8HoQ derivative 4 was subjected to a 100 ns molecular dynamics simulation, to confirm the structural stability and compactness of the GK–ligand complex. The FMO-derived molecular descriptors revealed an increase in hydrophilic nature and strong protein-binding affinities with respect to the position of carbonyl functional group substitutions. These findings, corroborated by molecular docking and in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling, indicate high intestinal absorption and suggest that suitable functional substitution in the quinoline ring makes promising candidates within the 8-HoQ system for evaluating pharmacological suitability.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

An in-silico investigation of 8-hydroxyquinoline (8-HoQ) derivatives as potential anti-tuberculosis agents by targeting glutamate kinase

  • 期刊论文

  • 发表日期：

    2025年11月25日

查看全文
  • Malathi Marimuthu,
  • Selvakumar Balasubramanian,
  • Ramanan Balasubramanian Viswanathan,
  • Hari Prasad Parthiban,
  • Malathi Mahalingam,
  • Gayathri Kasirajan

摘要

The current study has detailed the computational methodologies to assess the therapeutic potential of carbonyl-substituted derivatives 1–4 of 8-hydroxyquinoline (8-HoQ). Various computational techniques, including density functional theory, global chemical descriptors and molecular docking, were applied to analyze the properties of the 8-HoQ derivatives and the interactions between them and target proteins. Molecular stability and reactivity were evaluated using frontier molecular orbital (FMO) and molecular electrostatic potential studies, while topological visualizations, such as electron localization function, localized orbital locator, reduced density gradient, and interaction region indicator, provided insights into molecular polar charge characteristics. Molecular reactive sites identified from these analyzes were utilized in molecular docking studies targeting Glutamate Kinase (GK), a previously untapped enzyme in tuberculosis treatment. The 8-HoQ derivatives 1–4 exhibited binding affinity of -6.8, -7.5, -7.2, and − 8.2 kcal mol⁻¹, respectively, which are higher than the standard ligand of L-Glutamic acid, demonstrating their potential as GK activators to inhibit Mycobacterium tuberculosis (mtb). The high binding score derivative 8HoQ derivative 4 was subjected to a 100 ns molecular dynamics simulation, to confirm the structural stability and compactness of the GK–ligand complex. The FMO-derived molecular descriptors revealed an increase in hydrophilic nature and strong protein-binding affinities with respect to the position of carbonyl functional group substitutions. These findings, corroborated by molecular docking and in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling, indicate high intestinal absorption and suggest that suitable functional substitution in the quinoline ring makes promising candidates within the 8-HoQ system for evaluating pharmacological suitability.