Structure based Virtual Screening of Rivastigmine Derivatives as Cholinesterase Inhibitors

Abstract

The interaction of large protein molecules with small drug molecules is studied through in-silico studies. The molecular docking and other important pharmacokinetic (ADMET) properties of the compounds were carried out with rivastigmine and its derivatives against protein bovine serum albumin (PDB: 4F5S) to describe their better protein-ligand interactions and binding affinities. Rivastigmine is a promising drug that is used to treat Alzheimer’s disease. But due to the increased drug resistance property, its use becomes less effective. Hence, better drugs with higher potency are needed against this Alzheimer’s disease. In order to design a more potent drug computationally, we have taken here 52 derivatives of rivastigmine and were docked against protein bovine serum albumin. Besides, quantum chemical parameters like HOMO-LUMO band gap energy and other important pharmacological analysis like ADMET studies were also carried out to predict better drug candidature. Molecular dynamics simulation and MMPBSA binding free energy calculations were also validated. From this computational study, 14 designed compounds were found to have better potency against Alzheimer’s disease.