Flavone Hydrazide Thiourea Derivatives: Synthesis, anti-diabetic, and in silico QSAR Analysis

Abstract

This study reports synthesis of Flavone Hydrazide Thiourea Derivatives 2-21 with diverse functionalities for the cure of diabetic mellitus and their α-glucosidase inhibitor and in silico (computational) studies. In this regard, Flavone derivatives 2-21 has synthesized according to scheme and characterized by various spectroscopic techniques. These compounds showed significant potential towards α-glucosidase enzyme inhibition activity and found to be many fold better active than the standard Acarbose (IC50 =39.45±0.11µM). The IC50 values ranges 1.09-38.1µM. Among these, Compound 2 (IC50 = 3.16 ±0.29 µM) and 3 (IC50 = 2.12 ±0.78 µM) showed marvelous inhibition activity. Both these derivatives have –OH substitution at ring D. The molecular docking analysis revealed that these molecules have high potential to interact with the protein molecule and have high ability to bind with the enzyme. Furthermore, the computational study regarding drug likeness of molecules were also performed. The physicochemical and pharmacokinetics study showed that these compounds have excellent parameters required for drug likeness. The derivatives have high ability by GI absorption.