Sohrabi Marzieh, Binaeizadeh Mohammad Reza, Iraji Aida, Larijani Bagher, Saeedi Mina, Mahdavi Mohammad
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences Tehran Iran
School of Chemistry, College of Science, University of Tehran Tehran Iran.
RSC Adv. 2022 Apr 20;12(19):12011-12052. doi: 10.1039/d2ra00067a. eCollection 2022 Apr 13.
Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and has emerged as a controversial public health issue worldwide. The increasing number of patients with T2DM on one hand, and serious long-term complications of the disease such as obesity, neuropathy, and vascular disorders on the other hand, have induced a huge economic impact on society globally. In this regard, inhibition of α-glucosidase, the enzyme responsible for the hydrolysis of carbohydrates in the body has been the main therapeutic approach to the treatment of T2DM. As α-glucosidase inhibitors (α-GIs) have occupied a special position in the current research and prescription drugs are generally α-GIs, researchers have been encouraged to design and synthesize novel and efficient inhibitors. Previously, the presence of a sugar moiety seemed to be crucial for designing α-GIs since they can attach to the carbohydrate binding site of the enzyme mimicking the structure of disaccharides or oligosaccharides. However, inhibitors lacking glycosyl structures have also shown potent inhibitory activity and development of non-sugar based inhibitors is accelerating. In this respect, anti-α-glucosidase activity of metal complexes has attracted lots of attention and this paper has reviewed the inhibitory activity of first-row transition metal complexes toward α-glucosidase and discussed their probable mechanisms of action.
2型糖尿病(T2DM)的特征是血糖水平高,已成为全球有争议的公共卫生问题。一方面,T2DM患者数量不断增加,另一方面,该疾病严重的长期并发症如肥胖、神经病变和血管疾病,对全球社会造成了巨大的经济影响。在这方面,抑制α-葡萄糖苷酶(负责体内碳水化合物水解的酶)一直是治疗T2DM的主要治疗方法。由于α-葡萄糖苷酶抑制剂(α-GIs)在当前研究中占据特殊地位且处方药一般为α-GIs,研究人员受到鼓舞去设计和合成新型高效抑制剂。以前,糖部分的存在似乎对设计α-GIs至关重要,因为它们可以附着在酶的碳水化合物结合位点上,模仿二糖或寡糖的结构。然而,缺乏糖基结构的抑制剂也显示出强大的抑制活性,非糖基抑制剂的开发正在加速。在这方面,金属配合物的抗α-葡萄糖苷酶活性引起了很多关注,本文综述了第一排过渡金属配合物对α-葡萄糖苷酶的抑制活性,并讨论了它们可能的作用机制。