Scholarlink

Background <p>Drug discovery uses <i>in silico</i> biological activity prediction as a tool since it helps prioritise which molecules to test in vivo or in vitro. The <i>in silico</i> prioritization of new-fangled benzoxazole derivatives for their possible therapeutic action against CNS disorders is reported in this study.</p> Materials and Methods <p>Molecular docking simulations were performed on the GABA_Diazepam site (PDB ID: 6 × 3X) using Glide XP (Schrödinger 2020-4). Ligand structures, designed with ChemDraw, underwent <i>in silico</i> analysis by QikProp (Schrödinger 2020-4) was used for physicochemical property predictions.</p> Results and Discussion <p>The study examined nitrogen-substituted benzoxazole derivatives for potential use in CNS disorders by assessing their binding affinities, pharmacokinetics, and toxicity. Docking scores (MMGBSA) ranged from − 34.30 to -56.22&#xa0;kcal/mol, by way of compound 3 having the highest likeness (-56.22&#xa0;kcal/mol), while diazepam, the reference drug, showed the strongest binding (-68.77&#xa0;kcal/mol). Key connections with vital amino acids like MET286, PHE289, VAL290, and ASN265 helped stabilize the compounds in the binding site. This is also shown by Diazepam Pharmacokinetic properties predicted by QikProp indicated that most compounds followed Lipinski’s rule of 5, signifying they include good drug-like characteristics. They also showed acceptable solubility and brain/blood partitioning, indicating potential for CNS targeting. Toxicity predictions showed no significant risk of cardiotoxicity through HERG channel inhibition. Overall, these derivatives appear to be promising candidates for further study as potential CNS drugs.</p> Conclusion and Future Perspective <p>The nitrogen-substituted benzoxazole compounds under investigation demonstrate significant potential as CNS-active drugs, as indicated by favorable toxicity profiles, ADME properties, and molecular docking results. To build on these results, focused in vitro and in vivo studies are essential. Radioligand binding assays can validate binding affinity to the GABA receptor and assess receptor occupancy at therapeutically relevant doses. Additionally, pharmacodynamic evaluations using behavioral models, such as the elevated plus maze and rotarod test, can elucidate their sedative, anxiolytic, and anticonvulsant effects. These steps will provide critical insights into their therapeutic efficacy and support further development for CNS-related disorders.</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

In Silico Prediction, Molecular Docking Study for Identification of Novel Nitrogen Substituted Benzoxazole Derivative for Their Potential Biological Activity

  • 期刊论文

  • 发表日期：

    2025年2月13日

查看全文
  • Hemant U. Chikhale,
  • Dinesh D. Rishipathak

摘要

Background

Drug discovery uses in silico biological activity prediction as a tool since it helps prioritise which molecules to test in vivo or in vitro. The in silico prioritization of new-fangled benzoxazole derivatives for their possible therapeutic action against CNS disorders is reported in this study.

Materials and Methods

Molecular docking simulations were performed on the GABA_Diazepam site (PDB ID: 6 × 3X) using Glide XP (Schrödinger 2020-4). Ligand structures, designed with ChemDraw, underwent in silico analysis by QikProp (Schrödinger 2020-4) was used for physicochemical property predictions.

Results and Discussion

The study examined nitrogen-substituted benzoxazole derivatives for potential use in CNS disorders by assessing their binding affinities, pharmacokinetics, and toxicity. Docking scores (MMGBSA) ranged from − 34.30 to -56.22 kcal/mol, by way of compound 3 having the highest likeness (-56.22 kcal/mol), while diazepam, the reference drug, showed the strongest binding (-68.77 kcal/mol). Key connections with vital amino acids like MET286, PHE289, VAL290, and ASN265 helped stabilize the compounds in the binding site. This is also shown by Diazepam Pharmacokinetic properties predicted by QikProp indicated that most compounds followed Lipinski’s rule of 5, signifying they include good drug-like characteristics. They also showed acceptable solubility and brain/blood partitioning, indicating potential for CNS targeting. Toxicity predictions showed no significant risk of cardiotoxicity through HERG channel inhibition. Overall, these derivatives appear to be promising candidates for further study as potential CNS drugs.

Conclusion and Future Perspective

The nitrogen-substituted benzoxazole compounds under investigation demonstrate significant potential as CNS-active drugs, as indicated by favorable toxicity profiles, ADME properties, and molecular docking results. To build on these results, focused in vitro and in vivo studies are essential. Radioligand binding assays can validate binding affinity to the GABA receptor and assess receptor occupancy at therapeutically relevant doses. Additionally, pharmacodynamic evaluations using behavioral models, such as the elevated plus maze and rotarod test, can elucidate their sedative, anxiolytic, and anticonvulsant effects. These steps will provide critical insights into their therapeutic efficacy and support further development for CNS-related disorders.