• ISSN : 2231 - 0541 (Online)
  • 0976 - 3090 (print)
  • NLM ID : 101613942
  • CAS CODEN : PHARN8
  • Frequency : Bi-Monthly

IN SILICO DESIGN AND ADMET PREDICTION OF RIVASTIGMINE ANALOGUES FOR TREATMENT OF ALZHEIMER'S DISEASE

IN SILICO DESIGN AND ADMET PREDICTION OF RIVASTIGMINE ANALOGUES FOR TREATMENT OF ALZHEIMER'S DISEASE

Alzheimer's disease (AD) is the most prevalent, complex neurodegenerative disorder of the central nervous system, affecting over 20 million individuals worldwide. AD is a dementia- related disease which is characterized by t-protein aggregation, amyloid-ß deposits, oxidative stress and lowered levels of acetylcholine in the brain. Currently a few class of drugs such as Acetylcholinesterase (AChE) inhibitors, antioxidants, metal chelators, monoamine oxidase inhibitors, anti-inflammatory drugs and NMDA inhibitors are available and at best they offer some relief of symptoms. Presently, AChE inhibitors like Rivastigmine are the most effective therapy for AD. In this study, we analyzed seven Rivastigmine analogues de novo for pharmacokinetic profile (adsorption, distribution, metabolism and excretion) and toxicity by using Pre-ADMET tool which can predict physico-chemical, drug absorption and drug-like properties. The results showed that two Rivastigmine analogues (R=OH, R=Br) which showed good binding affinities for Acetyl cholinesterase (PDB ID: 1B41) exhibited more or similar ADME and toxicity properties in comparison to Rivastigmine. These designed analogues have the potential to become new lead compounds that might guide the design of drugs with optimized pharmacodynamic and pharmacokinetic properties in