Research Projects

This proposal aims to explore a unique approach to allosteric inhibition of acetylcholinesterase enzyme (AChE) activity using designed supra decorated bioactive compounds (ligands) utilizing tailored non-covalent interactions. AChE is a major target for most clinically used drugs for the treatment of neurodegenerative disorders. The proposal aims to design bioactive compounds with tailored supra-functionalities capable of developing intermolecular forces with targeted amino acid residues at regulatory sites of AChE for a desired pharmacological response. The synthetic segment of the project aims to develop supra decorated libraries of drug-like molecules using the reactive behavior of unsaturated systems, such as alkenes and alkynes, for targeted transformations. Photoredox catalysis will be used as an environmentally benign, broader substrate scope synthetic methodology with unprecedented reactivities and novel pathways to create exciting chemical motifs. In the chemico biological segment, the synthesized compounds will be comprehensively evaluated for acetylcholinesterase binding propensity using various biophysical methods, including the Michaelis-Menten enzyme kinetics model. In silico studies of molecular docking and simulations will be utilized for comprehensive mechanistic insights and corroboration of experimental observations. The project will also examine the ability of lead compounds to protect neuronal PC12 cells against induced damage by reactive oxygen species using the MTT assay.