Synthesis, molecular docking and design of Tetrahydroquinolines as acetylcholinesterase inhibitors

Margarita GutiÃÂÂ

Abstract

A series of tetrahydroquinolines (Compounds 1-8) were synthesized using Povarov reactions, subsequently characterized using spectroscopic methods and evaluated as Acetylcholinesterase/Butirylcholinesterase inhibitors. Bioinformatics tools analyzed active site interactions, leading to the design of a more active new compound. The most potent compound showed moderate in vitro activity (IC50 of 215μM) against AChE, while bioinformatics tools such as molecular docking and de novo design allowed establishment of binding sites and design of a new molecule with better activity, decreasing IC50 from 618 μM to 215μM. This study describes the application of bioinformatics tools in drug design.