Department of Medical Biology, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey.
Department of Medical Biology, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey; Department of Medical Biology, Institute of Health Sciences, University of Health Sciences, Istanbul, Turkey.
Comput Biol Chem. 2024 Oct;112:108180. doi: 10.1016/j.compbiolchem.2024.108180. Epub 2024 Aug 18.
Avicenna, a pioneer of modern medicine, recommended diuretic therapy to treat diabetes. Like Avicenna's approach, current medicine frequently prescribes oral antidiabetic pills with diuretic and hypoglycemic effects by blocking the absorption of sodium and glucose. To this end, the paper sought natural compounds with potential antidiabetic, cardioprotective, and diuretic properties through computer-based drug design (CADD) techniques, targeting the inhibition of SGLT2 proteins. We identified several bioactive compounds from various sources exhibiting potential multifunctionality through high-throughput virtual screening (HTVS) of vast compound libraries. Subsequent molecular docking and dynamics simulations were employed to assess these compounds' binding efficacy and stability with their respective targets, alongside ADMET prediction, to evaluate their pharmacokinetic and safety profiles. The top hits, phenylalanyltryptophan, tyrosyl-tryptophan, tyrosyl-tyrosine, celecoxib, and DIBOA trihexose, had superior docking scores ranging from -11,4 to -9,8 kcal/mol. The molecular dynamics simulations displayed steady interactions between target proteins and biocompounds throughout 100 ns without significant conformational shifts. These findings lay the groundwork for lead optimization and preclinical testing. This meticulous process ensures the safety and efficacy of potential treatments, marking a meaningful step toward developing innovative treatments for managing diabetes and its associated health complications.
阿维森纳是现代医学的先驱，他曾推荐利尿剂疗法来治疗糖尿病。与阿维森纳的方法类似，现代医学经常通过抑制钠和葡萄糖的吸收，开具有利尿和降血糖作用的口服抗糖尿病药。为此，本文通过计算机药物设计（CADD）技术，针对 SGLT2 蛋白的抑制作用，从各种来源中寻找具有潜在抗糖尿病、心脏保护和利尿特性的天然化合物。我们通过高通量虚拟筛选（HTVS）对大量化合物库进行筛选，从各种来源中鉴定出几种具有潜在多功能性的生物活性化合物。随后进行分子对接和动力学模拟，以评估这些化合物与各自靶标的结合效力和稳定性，并进行 ADMET 预测，以评估它们的药代动力学和安全性特征。排名靠前的命中化合物包括苯丙氨酰色氨酸、色氨酰色氨酸、酪氨酸酪氨酸、塞来昔布和 DIBOA 三己糖，它们的对接评分范围从-11.4 到-9.8 kcal/mol。分子动力学模拟显示，在 100 ns 的时间内，靶蛋白和生物化合物之间的相互作用稳定，没有明显的构象变化。这些发现为先导化合物的优化和临床前测试奠定了基础。这一细致的过程确保了潜在治疗方法的安全性和有效性，为开发治疗糖尿病及其相关健康并发症的创新疗法迈出了有意义的一步。
