Rational drug repurposing for alzheimer's treatment using in-silico ligand and structure-based approaches

Abstract Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.

Currently Available Non-Balloon Devices

Obesity and metabolic syndrome are known to have an impact on the economy. Obesity and metabolic syndrome affect about 40% population in the America alone, and with about 400 million obese adults in the world, obesity is a global concern. Moreover, the prevalence of overweight children is increasing. Bariatric surgery remains the gold standard for the treatment of obesity; however, endoscopic approaches may have a significant role in the management of metabolic syndrome and obesity. Until recently, many endoscopic methods have been introduced; however, few methods are used in practice, whereas others are under experimental research. Endoscopists have an important role in the treatment of obesity because endoscopic therapies have demonstrated their safety and efficacy over the past few years. Endoscopic bariatric therapies can be categorized as follows: space occupying, malabsorption, and gastric volume reduction. In this review, we summarize the currently available non-balloon type endoscopic procedure.