CREATION OF NOVEL GENERATION INHIBITORS WITH POTENTIAL EFFECT AGAINST ALZHEIMER'S DISEASE

Abstract

Using fine organic synthesis methods and the latest capabilities of computational chemistry, for the first time, 2-(4-amino-6-phenyl-1,2,5,6-tetrahydro-1,3,5-triazine-2(1H)-ylidene)-malononitrile, which contains a triazine ring and various functional groups in the molecule, was synthesized without the presence of a catalyst through a one-step three-component reaction. Structural analyses were carried out using X-ray and Hirshfeld surface analysis, and it was determined that asymmetric molecules of 2-(4-amino-6-phenyl-1,2,5,6-tetrahydro-1,3,5-triazine-2(1H)-ylidene)-malononitrile and a dimethylformamide solvent molecule in the asymmetric unit crystallize as a racemate in the monoclinic P21/c space group. These molecules exhibit stereochemical activity at the carbon atoms where the triazine rings are attached to the phenyl ring. For the first time, theoretical predictions using Density Functional Theory calculations for the synthesis reaction of tetrahydro-s-triazine via a one-step three-component condensation without a catalyst were experimentally tested. Comprehensive theoretical-experimental studies were conducted using quantum chemical calculations to simulate these chemical reactions, leading to significant results. The synthesis under milder conditions and atom-efficient methods obtained through computer simulations further enhances the importance of this work. This compound has shown high inhibitory effects on acetylcholinesterase in living organisms, and multiple analyses, including "molecular docking" studies, have revealed that in the future, representatives of these inhibitors with different functional groups could potentially be used as drugs against epilepsy, Alzheimer’s, and other neurological diseases. © 2024 Elsevier B.V., All rights reserved.