Synthesis and Exploration of New Imidazo4,5-cPyrazoles as Potent alpha-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 imidazo4,5-cpyrazoles was synthesized via simple versatile straightforward synthetic routes and was estimated for their in vitro a-amylase inhibition activity. The findings revealed that diphenylaminomethyl and phenylcarbamodithioate derivatives elicited potent a-amylase inhibition activities with IC50 values of 0.071 and 0.083 mu M, respectively that were comparable to acarbose (IC50 0.060 mu M). 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.