Potential Molecular Docking of Four Acetylcholinesterase Inhibitors
Journal Title: Drug Designing & Intellectual Properties International Journal - Year 2018, Vol 2, Issue 3
Abstract
Molecular modeling attempts to study the function, structure and inhibition of the acetylcholinesterase enzyme due to the fact that the inhibition of this enzyme is importance to medical conditions such as Alzheimer’s disease, myasthenia gravis and Parkinson’s disease, and it is also important in eminent toxicological susceptibility to nerve agents. In this study we present an approach for forecasting the inhibitory activity of acetylcholinesterase (AChE) inhibitors by using docking studies. The docking studies were done on acetylcholinesterase to attain the conformation of the enzyme in water surroundings. The obtained conformation of the enzyme was used for docking with four inhibitors (physostigmine, neostigmine, pyridostigmine and rivastigmine). Docking analysis showed that hydrogen bonds and hydrophobic interactions play important tasks in the acetylcholinesterase -inhibitor complex. Subsequently, all inhibitors that bind at the catalytic site of acetylcholinesterase and their interactions with acetylcholinesterase were studied. In addition, conformation stability of acetylcholinesterase -inhibitors was studied using simulation docking technique. The complex showed that acetylcholinesterase conformation did not change significantly in the presence of the four inhibitors. This paper showed important studies on acetylcholinesterase and assists to illuminate the four inhibitors interdependencies using molecular modeling. Acetylcholine (ACh) is a neurotransmitter broadly distributed in the central and peripheral, autonomic nervous system (CNS). In the CNS, ACh performs several functions, such as memory, learning, motor control and attention. Acetylcholinesterase (AChE), one of the most essential enzymes in the family of serine hydrolases, catalyzes the hydrolysis of neurotransmitter acetylcholine, which plays an important role in memory and cognition [1-4]. It has been suggested that acetylcholinesterase (AChE) degrades the esters of choline and has a role in neurotransmission within the autonomic and somatic motor nervous systems and it is the target of action of the drugs (inhibitors) such as physostigmine, neostigmine, pyridostigmine and rivastigmine, physostigmine [1-4]. It is well known that AChE enzyme regulated the release and entrance of ACh in cholinergic fibers [5]. The function of AChE in neurological disorders like Myasthenia gravis (MG) [6], Alzheimer’s disease [7], Parkinson’s disease [8] and other ‘non-classical’ activities such as, neurite formation, network formation and cell adhesion [9] draw attention of many researches related to the medical field. The exact mechanisms of the interaction of physostigmine, neostigmine, pyridostigmine and rivastigmine with the acetylcholinesterase receptor complex still need further molecular modeling studies.
Authors and Affiliations
Nahd Mohamed Elmaki, Inass A Al Sadawi, Anton Hermann, Abdul M Gbaj
Keywords
Related Articles
- EP ID EP588181
- DOI 10.32474/DDIPIJ.2018.02.000136
- Views 172
- Downloads 0
Current Challenges and Obstacles to Drug Development for Chagas Disease
Chagas disease is a protozoan infection which was first identified more than one hundred years ago. But even now, drugs to treat the latent and chronic phases of the disease are not available. The success of a drug desig...
An Overview on Niosomes: A Drug Nanocarrier
Niosome are non-ionic surfactant vesicles acquired on hydration of synthetic nonionic surfactants, with or without consolidation of cholesterol or their lipids. They are vesicular systems like liposome’s that...
Ionic Liquid Technology: A Budding Innovative Podium for the Pharmaceutical Industry
Ionic liquids considered to be a reasonably current magical chemical due their unique properties, have a large variety of applications in all areas of the chemical and pharmaceutical industries. The areas of application...
From Merck's CCK- Antagonists Via 4-Amino-2(5H)- Furanones towards 5-Hydroxy-Pyrrol-2-Ones: Design, Synthesis and Evaluation of PNB-001 & PNB-081 as Experimental Therapeutic Agents in Pain Management
Arylated 5-hydroxy-pyrrol-2-ones were prepared in 2 synthetic steps from muco-chloric acid and were optimised as CCK / CCK2 selective ligands using radio labelled binding assays. A potent CCK selective ligand was identif...
Regulatory Inflation in Pharmaceutical Drug Development?
During the last decade, and exponentially over the last three years, numerous pharmaceutical manufacturing plants have closed their doors following current Good Manufacturing Practices (cGMP) audits from various agencies...