Structure-activity Relationships of Natural and Synthetic Indole-derived Scaffolds as α-Glucosidase Inhibitors: A Mini-review

α-Glucosidase plays an important role in carbohydrate metabolism and is an attractive drug target for the treatment of diabetes, obesity and other related complications. Currently, acarbose, miglitol and voglibose have been approved by FDA as treatment of diabetes by oral α-glucosidase inhibitors. With the development of anti-diabetic drugs, the emergence of novel drugs with various chemotypes has overshadowed α-glucosidase inhibitors. Since 1990s, FDA has not approved new chemical entities against αglucosidase, which resulted in restricted clinical medication. Nevertheless, this type of inhibitors possessed several unparalleled advantages over other drugs, especially mild side effects (non-systemic gastrointestinal side effects and occasional allergic reactions). Additionally, α-glucosidase inhibitors for monotherapy or in combination with other drugs have been proved to be a feasible approach for the treatment of diabetes. In the last decade, the discovery of natural or synthetic indole derivatives possessing the inhibitory activity of α-glucosidase has received great attentions. Herein, we summarized indoles as inhibitors of α-glucosidase activity, their mechanism of action, synthetic methodologies and structure-activity relationships. Moreover, we compared the inhibitory potencies of all compounds under their corresponding positive control as well as oral absorption in silico evaluated by tPSA. This review will provide a medium on which future drug design and development for the treatment of diabetes may be modelled as many drug candidates highlighted and present great potential as an effective anti-diabetic chemotherapy.

Keywords: Anti-diabetic agents; Enzyme inhibitors; Indole; Structure-activity relationship; Synthetic route.; α-Glucosidase.