Scientific Reports ( IF 3.8 ) Pub Date : 2023-02-01 , DOI: 10.1038/s41598-023-28828-1 Anam Rubbab Pasha 1, 2 , Ajmal Khan 2 , Saeed Ullah 2, 3 , Sobia Ahsan Halim 2 , Javid Hussain 4 , Muhammad Khalid 5, 6 , Muhammad Moazzam Naseer 7 , Attalla F El-Kott 8, 9 , Sally Negm 10, 11 , Ahmed Al-Harrasi 2 , Zahid Shafiq 1, 12
Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a–y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC50 values in range of 2.14–115 µM as compared to acarbose used as control. Additionally, all the compounds were docked at the active site of α-glucosidase to predict their mode of binding. The docking results indicates that Glu277 and Asn350 play important role in the stabilization of these compounds in the active site of enzyme. These molecules showed excellent predicted pharmacokinetics, physicochemical and drug-likeness profile. The anti-diabetic potential of these molecules signifies their medical importance and provide insights into prospective therapeutic options for the treatment of T2DM.
中文翻译:
新型二苯基脲偶联亚胺类似物的合成及其在体外和计算机模拟方法中对糖尿病管理的意义
II 型糖尿病 (T2DM) 是一个全球性的健康问题,患病率很高。α-葡萄糖苷酶的抑制在 T2DM 的管理中具有最重要的意义。本研究旨在合成 1,3-二苯基脲 ( 3a–y ) 的席夫碱,并通过抑制α -葡萄糖苷酶(碳水化合物分解代谢的关键参与者)来研究其体外抗糖尿病能力。所有化合物的结构均通过各种技术确认,包括傅立叶变换红外光谱 (FTIR) 和核磁共振 (NMR) 以及质谱 (MS) 方法。有趣的是,所有这些化合物都显示出有效的抑制作用 IC 50与用作对照的阿卡波糖相比,值在 2.14–115 µM 范围内。此外,所有化合物都停靠在α-葡萄糖苷酶的活性位点以预测它们的结合模式。对接结果表明,Glu277 和 Asn350 在这些化合物在酶活性位点的稳定中起重要作用。这些分子显示出出色的预测药代动力学、物理化学和药物相似性特征。这些分子的抗糖尿病潜力表明了它们的医学重要性,并为治疗 T2DM 的前瞻性治疗选择提供了见解。