Molecular Dynamic Simulations of Dual Inhibitors for AChE and BChE; Theoretical and Experimental Approaches

Abstract

The aim of the study is to design and synthesize thiazolidinone derivatives having therapeutic potential using PABA as a core component. The characterization of thiazolidinones MS1–MS6was carried out using different spectroscopic techniques before being subjected to DFT studies to calculate various parameters such as HOMO/LUMO energy gaps and global chemical properties. Thiazolidinones MS1–MS6were screened to evaluate their in vitro enzyme inhibition potential. In addition to experimental work, theoretical approaches were used as supporting components to design the enzyme inhibitors. In-silico ADMET and docking studies were performed to check the therapeutic properties of thiazolidinone derivatives. The enzyme inhibition potential predicted that MS1–MS6have potential to inhibit AChE and BChE. The highest activity was depicted by MS4 with a percentage inhibition of 81.7 ±1.1% against AChE. The molecular dynamic simulation was run for MS4 showing a similar activity on enzyme compared to the standard inhibitor. Both experimental and theoretical assessments suggested the therapeutic importance of the thiazolidinone derivatives MS1–MS6. In-depth studies are ongoing to complete therapeutic probing in terms of toxicity and chemical uses.