Choudhury Abbas Alam, Arumugam Mohanapriya, Ponnusamy Nirmaladevi, Sivaraman Dhanasekaran, Sertsemariam Woldie, Thiruvengadam Muthu, Pandiaraj Saravanan, Rahaman Mostafizur, Devi Rajeswari V
Department of Biomedical Sciences, School of Bio Sciences and Technology, VIT, Vellore, India.
Department of Biotechnology, School of Bio Sciences and Technology, VIT, Vellore, India.
J Biomol Struct Dyn. 2024 Feb 9:1-15. doi: 10.1080/07391102.2024.2313156.
Diabetes mellitus (DM) is a multifactorial life-threatening endocrine disease characterized by abnormalities in glucose metabolism. It is a chronic metabolic disease that involves multiple enzymes such as α-amylase and α-glucosidases. Inhibition of these enzymes has been identified as a promising method for managing diabetes, and researchers are currently focusing on discovering novel α-amylase and α-glucosidase inhibitors for diabetes therapy. Hence, we have selected 12 bioactive compounds from the (MC) plant and performed a virtual screening and molecular dynamics investigation to identify natural inhibitors of α-amylase and α-glucosidases. Our result revealed that phytocompound Rutin showed the highest binding affinity against α-amylase (1HNY) enzymes at (-11.68 kcal/mol), followed by Karaviloside II (-9.39), Momordicoside F (-9.19), Campesterol (-9.11. While docking against α-glucosidases (4J5T), Rutin again showed the greatest binding affinity (-11.93 kcal/mol), followed by Momordicine (-9.89), and Campesterol (-8.99). Molecular dynamics (MD) simulation research is currently the gold standard for drug design and discovery. Consequently, we conducted simulations of 100 nanoseconds (ns) to assess the stability of protein-ligand complexes based on parameters like RMSD, RMSF, RG, PCA, and FEL. The significance of our findings indicates that rutin from MC might serve as an effective natural therapeutic agent for diabetes management due to its strongest binding affinities with α-amylase and α-glucosidase enzymes. Further research in animals and humans is essential to validate the efficacy of these drug molecules.
糖尿病（DM）是一种多因素的危及生命的内分泌疾病，其特征是葡萄糖代谢异常。它是一种慢性代谢疾病，涉及多种酶，如α-淀粉酶和α-葡萄糖苷酶。抑制这些酶已被确定为治疗糖尿病的一种有前景的方法，研究人员目前正专注于发现用于糖尿病治疗的新型α-淀粉酶和α-葡萄糖苷酶抑制剂。因此，我们从（MC）植物中选择了12种生物活性化合物，并进行了虚拟筛选和分子动力学研究，以鉴定α-淀粉酶和α-葡萄糖苷酶的天然抑制剂。我们的结果显示，植物化合物芦丁对α-淀粉酶（1HNY）酶表现出最高的结合亲和力（-11.68千卡/摩尔），其次是卡拉维苷II（-9.39）、苦瓜苷F（-9.19）、菜油甾醇（-9.11）。在与α-葡萄糖苷酶（4J5T）对接时，芦丁再次表现出最大的结合亲和力（-11.93千卡/摩尔），其次是苦瓜碱（-9.89）和菜油甾醇（-8.99）。分子动力学（MD）模拟研究目前是药物设计和发现的金标准。因此，我们基于均方根偏差（RMSD）、均方根波动（RMSF）、回旋半径（RG）、主成分分析（PCA）和自由能景观（FEL）等参数进行了100纳秒（ns）的模拟，以评估蛋白质-配体复合物的稳定性。我们研究结果的意义表明，由于芦丁与α-淀粉酶和α-葡萄糖苷酶具有最强的结合亲和力，来自MC的芦丁可能作为一种有效的天然治疗剂用于糖尿病管理。在动物和人类中进行进一步研究对于验证这些药物分子的疗效至关重要。
