Quercetin analogs as α-glucosidase inhibitors with antidiabetic activity

Abstract

This study investigated the inhibitory effects of synthesized quercetin analogs (Q1–Q23) on α-glucosidase, particularly Q7. Q7, a synthetic analog of quercetin, exhibits superior α-glucosidase inhibitory properties compared with quercetin and the standard drug acarbose. This effect is attributed to the unique –CF3 group on the benzene ring of Q7, which enhances its inhibitory effect. As a non-competitive inhibitor, Q7 shows strong binding and stability within the α-glucosidase-Q7 complex. In vivo experiments showed that Q7 significantly reduced fasting blood sugar levels in diabetic mice, surpassing the effects of metformin. In addition, it affects the gut microbiota, particularly the microbes associated with anti-inflammatory responses and short-chain fatty acid production, which are crucial for the treatment of type 2 diabetes. However, the current Q7 dosage led to carbohydrate accumulation in the colon of mice, impairing the function of the intestinal microbiota. This study highlights the potential of Q7 for treating type 2 diabetes and emphasizes the need to determine the optimal dosages that balance therapeutic effects and gut health.