In-Silico Investigational Study of Pyrido-acridine Congener Amphimedine against Alzheimer’s Disease

To investigate in-silico result of potent phytocomponent amphimedine against Alzheimer’s disease as Glycogen synthase kinase-3 inhibitor.

The neurodegenerative illnesses Parkinson's disease (PD) and Alzheimer's disease (AD) have become two of the most significant health issues of the twenty-first century. The drugs currently used to treat AD and PD are ineffective and have side effects. One of the most important and conservative sources of medications for treating neurological issues is natural goods.

A Pyrido-acridines congener is amphimedine. However, a thorough investigation into amphimedine's impact on AD has yet to be conducted. Numerous in silico investigations, beginning with molecular docking against glycogen synthase kinase-3 for AD, were performed to assess the neuroprotective impact of amphimedine. Utilizing the software Auto Dock 4.1, the results were contrasted with those of three conventional medications. Amphimedine's physiochemical characteristics, including the Lipinski rule of five, drug-likeness, and factors like its absorption, distribution, metabolism, elimination, and toxicity (ADMET) profiles, were also investigated. With acceptable ADMET profiles for therapeutic usage, Amphimedine conforms to all five of Lipinski's parameter.

Autodock tools carried out the docking investigation. On the RCSB website, the necessary proteins have been downloaded. The ProTox-II service projected its toxicity category.

The phytocompound has strong affinityfor 1Q5K as GSK-3 blocker. The molecule's toxicology has been examined. As a result, we now recognize that this scaffold solely exhibits immunotoxicity and falls into toxicity class 4.

In comparison to currently prescribed standard medications, the docking results (kcal/mol) demonstrated relatively better effectiveness against AD-related targets. Overall, molecular docking's potential binding affinity and additional multiparametric drug-ability profiles imply that amphimedine might be a good therapeutic lead for treating AD. However, employing amphimedine as a prospective medicine against AD treatment requires more clinical and in vivo investigations, where the in-silico data are more beneficial to speed up drug design.