Design, synthesis, and evaluation of the rhodanine-3-propanoic acid-phenoxy-1,2,3-triazole-acetamide derivatives as active agents against α-glucosidase, α-amylase, and protein tyrosine phosphatase 1B

Abstract

In an effort to explore a new class of anti-diabetic agents, a series of rhodanine-3-propanoic acid-phenoxy-1,2,3triazole-acetamide derivatives (compounds 3a-m) were designed, synthesized, and characterized. The synthesized compounds 3a-m were evaluated for their in vitro inhibitory activities against alpha-glucosidase, alpha-amylase, and protein tyrosine phosphatase 1B (PTP1B). The experimental data demonstrated that all the synthesized compounds were more potent than the standard inhibitor acarbose against both alpha-glucosidase and alpha-amylase. Specifically, the 2,4-chloro derivative (3h) and the 4-ethyl derivative (3e) were the most potent compounds against alpha-glucosidase and alpha-amylase, with IC50 values 6.66 mu M and 23.38 mu M, respectively, while IC50 values of acarbose as a standard inhibitor against alpha-glucosidase and alpha-amylase were 61.37 mu M and 123.60 mu M, respectively. Moreover, the synthesized compounds showed moderate to weak inhibitory activities against PTP1B in comparison with the standard inhibitor suramin. The observed inhibitory activities of compounds 3h and 3e against alpha-glucosidase and alpha-amylase were further supported by molecular docking studies on these enzymes. Additionally, the evaluation of drug-likeness and the prediction of ADMET profiles suggested that these compounds possess good oral bioavailability and a favorable toxicity profile.