Ghasemi Mehran, Iraji Aida, Dehghan Maryam, Lotfi Nosood Yazdanbakhsh, Irajie Cambyz, Bagherian Khouzani Nafiseh, Mojtabavi Somayeh, Faramarzi Mohammad Ali, Mahdavi Mohammad, Al-Harrasi Ahmed
Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box 33, Birkat Al Mauz, Nizwa, Oman.
Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Bioorg Chem. 2024 Dec;153:107908. doi: 10.1016/j.bioorg.2024.107908. Epub 2024 Oct 29.
In this study, a series of fifteen compounds (7a-o) based on a quinoline-benzimidazole scaffold bearing piperazine acetamide derivatives were synthesized and evaluated for their potential as α-glucosidase inhibitors, which are important therapeutic agents in the management of type 2 diabetes mellitus. Among the synthesized compounds, 7m exhibited the most potent inhibitory activity, demonstrating a 28-fold greater efficacy than the standard clinical inhibitor, acarbose. Molecular docking studies indicated strong binding interactions between 7m and the α-glucosidase active site, including hydrogen bonding, π-π stacking, and π-cation interactions. Furthermore, molecular dynamics simulations revealed that compound 7m formed a highly stable complex with the enzyme. These findings suggest that compound 7m is a promising candidate for further development as an effective antidiabetic agent, offering valuable insights into the design of potent α-glucosidase inhibitors based on the quinoline-benzimidazole framework.
在本研究中，合成了一系列基于带有哌嗪乙酰胺衍生物的喹啉 - 苯并咪唑骨架的十五种化合物（7a - o），并评估了它们作为α - 葡萄糖苷酶抑制剂的潜力，α - 葡萄糖苷酶抑制剂是治疗2型糖尿病的重要治疗药物。在合成的化合物中，7m表现出最有效的抑制活性，其效力比标准临床抑制剂阿卡波糖高28倍。分子对接研究表明7m与α - 葡萄糖苷酶活性位点之间存在强烈的结合相互作用，包括氢键、π - π堆积和π - 阳离子相互作用。此外，分子动力学模拟表明化合物7m与该酶形成了高度稳定的复合物。这些发现表明化合物7m作为一种有效的抗糖尿病药物具有进一步开发的潜力，为基于喹啉 - 苯并咪唑骨架设计有效的α - 葡萄糖苷酶抑制剂提供了有价值的见解。
