Exploring the Potential of Avenanthramides and their Analogues as α-Glucosidase Inhibitors for Type 2 Diabetes Treatment Utilizing Virtual Screening, Molecular Dynamics, and Drug-likeness Predictions

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL
Assia Guendouze, El Hassen Mokrani, Ouided Benslama, Sabrina Lekmine
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Abstract

Background: Optimal glycemic control is crucial in type 2 diabetes treatment, with αglucosidase inhibitors emerging as promising candidates. Avenanthramides, compounds found in oats, exhibit therapeutic potential, but their efficacy as α-glucosidase inhibitors requires thorough evaluation. Objective: This study investigates the potential of avenanthramides and their derivatives as inhibitors of α-glucosidase for the treatment of type 2 diabetes through comprehensive computational analysis. Methods: Structure-Based Virtual Screening of 3543 avenanthramides and their analog compounds was conducted using FlexX. The top 30 ranked compounds were subjected to visual inspection of their binding mode within the α-glucosidase binding site to eliminate false positives. The top-ranked molecule was subjected to dynamic simulation and ADMET prediction. Results: The results revealed that 1634 compounds were found to exhibit a greater α-glucosidase inhibitory potency than miglitol, the reference molecule. Compound S1 exhibited superior αglucosidase inhibitory potency with a binding energy of -45.7786 kJ/mol compared to miglitol, which had a binding energy of -26.5186 kJ/mol. S1 was predicted to occupy the entire binding site with an optimized number of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations demonstrated that S1 had a lower average RMSD (0.15 ± 0.01 nm) compared to miglitol (0.16 ± 0.01 nm), indicating superior stability within the α-glucosidase binding site. S1 exhibited favorable drug-like properties, suggesting its potential as a lead compound for further development in type 2 diabetes treatment. Conclusion: These findings highlight S1's potential for diabetes treatment and pave the way for future experimental investigations. The computational approach utilized offers valuable insights into the inhibitory potential of avenanthramides, providing a foundation for further drug development for type 2 diabetes.
利用虚拟筛选、分子动力学和药物相似性预测探索金刚烷酰胺及其类似物作为 α-葡萄糖苷酶抑制剂治疗 2 型糖尿病的潜力
背景:最佳的血糖控制是 2 型糖尿病治疗的关键,α-葡萄糖苷酶抑制剂是很有前景的候选药物。燕麦中的化合物 Avenanthramides 具有治疗潜力,但其作为 α-葡萄糖苷酶抑制剂的功效需要全面评估。研究目的本研究通过全面的计算分析,探讨了燕麦酰胺及其衍生物作为α-葡萄糖苷酶抑制剂治疗2型糖尿病的潜力。研究方法使用 FlexX 对 3543 种芒草酰胺及其类似化合物进行了基于结构的虚拟筛选。对排名前 30 位的化合物在 α-葡萄糖苷酶结合位点内的结合模式进行目测,以消除假阳性。对排名第一的分子进行动态模拟和 ADMET 预测。结果显示结果显示,有 1634 个化合物比参考分子米格列醇表现出更强的α-葡萄糖苷酶抑制效力。化合物 S1 表现出更强的α-葡萄糖苷酶抑制效力,其结合能为-45.7786 kJ/mol,而米格列醇的结合能为-26.5186 kJ/mol。根据预测,S1 可通过优化的氢键和疏水相互作用占据整个结合位点。分子动力学模拟表明,与米格列醇(0.16 ± 0.01 nm)相比,S1 的平均 RMSD(0.15 ± 0.01 nm)更低,这表明它在α-葡萄糖苷酶结合位点内具有更高的稳定性。S1 表现出了良好的类药物特性,这表明它有可能成为一种先导化合物,用于 2 型糖尿病治疗的进一步开发。结论这些发现凸显了 S1 治疗糖尿病的潜力,并为今后的实验研究铺平了道路。所采用的计算方法为了解文竹酰胺的抑制潜力提供了宝贵的见解,为进一步开发治疗 2 型糖尿病的药物奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
1.80
自引率
10.00%
发文量
245
审稿时长
3 months
期刊介绍: Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
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