Synthesis and evaluation of aryl aminomethylene substituted barbiturates and thiobarbiturates as novel α-amylase inhibitors and radical scavengers

A widespread increase in people affected by diabetes mellitus (DM) has led to the development of new strategies to combat this disease. Targeting the activity of the α -amylase enzyme and preventing oxidative stress involved in the onset and progression of type 2 DM is considered to represent the most effective therapeutic strategy for treating metabolic disorders. In the course of developing α -amylase enzyme inhibitors and antioxidants, we synthesized aryl aminomethylene substituted barbiturates and thiobarbiturates by single-step condensation reaction. All synthetic compounds were confirmed by various spectral techniques such as EI-MS, HREI-MS, 1 H, and 13 C NMR. Synthetic barbiturates and thiobarbiturates were subjected to the assessment of their in vitro α -amylase inhibitory activity as well as DPPH and ABTS radical scavenging potential. It is worth noting that all analogs were found good to moderately active with the IC 50 values ranging from 1.62 ± 0.17 to 3.40 ± 0.19 µM for α -amylase, 0.55 ± 0.11 to 1.99 ± 0.04 µM for DPPH and 0.46 ± 0.34 to 2.01 ± 0.04 µM for ABTS as compared to standards acarbose (IC 50 = 1.46 ± 0.26 µM) and ascorbic acid (IC 50 = 0.45 ± 0.35 µM for DPPH; IC 50 = 0.43 ± 0.06 µM for ABTS), respectively. Molecular docking studies deciphered important key interactions of ligands with the active site of the enzyme. These identified α -amylase inhibitors as well as DPPH and ABTS radical scavengers may serve as potential lead candidates for the management of diabetes mellitus. Graphical abstract