Synthesis, characterization, biological activity and molecular docking studies of novel schiff bases derived from thiosemicarbazide: Biochemical and computational approach

Abstract

In this study, eight new Schiff base derivatives (2a-h) were synthesized and their inhibition activities against Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), alpha-Glucosidase and Lactoperoxidase (LPO) were investigated. Structures of the synthesized compounds were characterized using H-1 and C-13 nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and high-resolution mass spectrometry (HRMS) spectroscopic methods. AChE was inhibited by these novel Schiff bases (2a-h) in low nanomolar levels, the K-i of which differed between 592.66 +/- 57.04 and 810.78 +/- 84.06 nM. Against BChE, the novel compounds demonstrated Kis varying from 358.31 +/- 37.88 to 577.24 +/- 59.91 nM. Also, these novel Schiff bases effectively inhibited alpha-glucosidase, with K-i values in the range of 1.56 +/- 0.32 to 14.78 +/- 2.57 nM. For LPO, K-i values were in the range of 3.96 +/- 0.37 to 12.75 +/- 0.06 nM. For alpha-glucosidase, the most effective molecules were 2b and 2 g with K-i values of 1.56 +/- 0.32 and 14.78 +/- 2.57 nM, respectively. Molecular docking results showed that the compounds have binding affinity with -5.559,-9.698, -7.606, and -6.971 kcal/mol against LPO, AChE, BChE, and alpha-glucosidase enzyme, respectively. It has been observed that the furan and thiosemicarbazone moieties play an important role in the inhibition of these enzymes. (C) 2020 Elsevier B.V. All rights reserved.