Synthesis, acetylcholinesterase and butyrylcholinesterase inhibitory potential and molecular docking study of thiazole bearing thiourea analogues

Abstract

We have synthesized fourteen thiazole bearing thiourea derivatives (1-14), characterized through different techniques i.e., NMR, HR-EIMS and tested against acetylcholinesterase and butyrylcholinesterase inhibitory potentials. All analogues showed inhibitory potential having varied IC50 values ranged from 2.10 ± 0.02 to 109.40 ± 0.04 µM (for AChE) and 3.10 ± 0.01 to 102.20 ± 0.04 µM (for BuChE) as compared to standard drug Eserine (IC50 = 0.85 ± 0.0001 & 0.04 ± 0.0001 µM respectively). Among the series, analogues 6, 11, 7 and 12 displayed excellent inhibitory potential against acetylcholinesterase. Analogue 14 (IC50 = 3.10 ± 0.01 µM) was found to be most potent against butyrylcholinesterase. Structure activity relationship (SAR) was established depend upon nature, position and number of substituent/s attached to the phenyl ring of basic nucleus. Molecular docking study was carried out to check the binding interaction of most potent analogues with the active site of enzyme.