Investigating Antialzheimer Potential of Biogenic Compounds From Zinc 15 Database As NMDA Antagonist: A Insilico Approach.

Abstract

Abstract Alzheimer's disease is an unavoidable neurological disorder in which memory loss, cognitive decline, and eventual dementia are brought on by the death of brain cells. There is no recognized treatment for Alzheimer's illness. By the year 2050, it is expected that the global population will witness approximately 100 million cases of Alzheimer’s disease (AD). Despite recognizing AD as a formidable illness for over a century, no effective cure has been discovered thus far. Synaptic dysfunction could result from disturbed synaptic calcium handling caused by excessive activation of glutamate receptors, particularly the N-methyl-D-aspartate receptors (NMDARs). Glutamate serves as the main excitatory neurotransmitter in the brain, acting on both ionotropic and metabotropic glutamate receptors. In recent years, a number of pharmacologically active substances that were derived from plants, animals, and microbes have shown promise in the treatment of AD by focusing on various pathogenic processes. Initially, we used virtual screening to assess natural product-like compounds against NMDA receptors. In this research study, we have screened a natural compound database derived from zinc15. The best candidate was then validated through molecular dynamics simulation (MDS). The results revealed that out of 4221 compounds tested, only 165 showed superior binding interactions compared to native ligands, making them inhibitors for protein. Further analysis using ADMET indicates favorable drug-like properties, particularly for CNS drug-likeness. The MDS results, including RMSD, RMSF, Rg, and residue interactions, indicated a strong and stable association between top molecules and target protein. This confirms that top molecules can effectively remain within the binding pockets of the target proteins, forming stable protein-ligand complexes.