Synthesis and Exploration of New Imidazo4,5-cPyrazoles as Potent α-Amylase Inhibitors

摘要

To identify new leads of small molecules as a-amylase inhibitors, the current research is focused on the assessment of imidazopyrazoles. Hence, a set of novel imidazo[4,5-c]pyrazoles was synthesized via simple versatile straightforward synthetic routes and was estimated for their in vitro α-amylase inhibition activity. The findings revealed that diphenylaminomethyl and phenylcarbamodithioate derivatives elicited potent a-amylase inhibition activities with IC_(50) values of 0.071 and 0.083 μM, respectively that were comparable to acarbose (IC_(50) 0.060 μM). Molecular docking and in silico studies were performed for the most active derivatives and demonstrated that docked compounds have good binding affinities toward a-amylase with binding free energies that are very similar to that of acarbose. Furthermore, these compounds demonstrated not only significant biological activity but also noteworthy physicochemical properties, drug-likeness, and good pharmacokinetics. As a result, such compounds offered a robust opportunity for further development and optimization of the imidazopyrazole scaffold for the potential management of Type II Diabetes Mellitus.