Toobaei Zahra, Yousefi Reza, Panahi Farhad, Shahidpour Sara, Nourisefat Maryam, Doroodmand Mohammad Mahdi, Khalafi-Nezhad Ali
Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran; Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Carbohydr Res. 2015 Jun 26;411:22-32. doi: 10.1016/j.carres.2015.04.005. Epub 2015 Apr 18.
In this study a novel series of poly-hydroxyl functionalized acridine derivatives (L1-L9) was synthesized and their inhibitory activities against α-Glucosidase (α-Gls) and α-Amylase (α-Amy) were evaluated, spectroscopically. The synthetic compounds consist of three different substructures, including a 4-(4-aminophenoxy) phenyl group (R3), an acridine moiety (R2) and a poly-hydroxy chain (R1). The results indicate that among the synthetic compounds, L5 with a chromeno[3',4':5,6]pyrido[2,3-d]pyrimidine moiety demonstrates the highest inhibitory activity against both yeast and rat α-Gls enzymes. Also, L2 with the thioxo-pyrido[2,3-d:6,5-d'] dipyrimidine moiety plays an important role in the inhibition of yeast α-Gls. In addition, the results may suggest a significant role for the nature of sugar moiety of the synthetic compounds in their inhibitory action against α-Gls. Moreover, in comparison with Acarbose, which is a widely used anti-diabetic drug, these compounds show negligible inhibitory activity against pancreatic α-Amy, which is important in the term of their reduced susceptibility for possible development of the intestinal disturbance side effects. Results of this study may suggest these synthetic compounds as novel molecular templates for construction of potentially anti-diabetic drugs with the ability for more convenient management of postprandial hyperglycemia.
在本研究中，合成了一系列新型的多羟基官能化吖啶衍生物（L1-L9），并通过光谱法评估了它们对α-葡萄糖苷酶（α-Gls）和α-淀粉酶（α-Amy）的抑制活性。合成的化合物由三个不同的亚结构组成，包括一个4-(4-氨基苯氧基)苯基（R3）、一个吖啶部分（R2）和一个多羟基链（R1）。结果表明，在合成的化合物中，具有色烯并[3',4':5,6]吡啶并[2,3-d]嘧啶部分的L5对酵母和大鼠α-Gls酶均表现出最高的抑制活性。此外，具有硫代吡啶并[2,3-d:6,5-d']二嘧啶部分的L2在抑制酵母α-Gls方面发挥着重要作用。此外，结果可能表明合成化合物糖部分的性质在其对α-Gls的抑制作用中起重要作用。此外，与广泛使用的抗糖尿病药物阿卡波糖相比，这些化合物对胰腺α-Amy的抑制活性可忽略不计，这在降低其发生肠道紊乱副作用的可能性方面很重要。本研究结果可能表明这些合成化合物作为新型分子模板，可用于构建具有更方便管理餐后高血糖能力的潜在抗糖尿病药物。
