Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid

Abstract

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by ¹HNMR, ¹³CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC₅₀ = 12.84 ± 0.52 µM), 4 (IC₅₀ = 13.64 ± 0.58 µM), 12 (IC₅₀ = 15.73 ± 0.71 µM), 13 (IC₅₀ = 16.62 ± 0.47 µM), 15 (IC₅₀ = 17.40 ± 0.74 µM), 3 (IC₅₀ = 18.45 ± 1.21 µM), 7 (IC₅₀ = 19.68 ± 0.82 µM), and 2 (IC₅₀ = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC₅₀ = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.