Computer-aided Drug Design Applied to Parkinson Targets

• Published in: Current neuropharmacology Vol. 16; no. 6; pp. 865 - 880
• Main Authors: Ishiki, Hamilton M, Filho, Jose Maria Barbosa, da Silva, Marcelo S, Scotti, Marcus T, Scotti, Luciana
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.01.2018; Benham Science Publishers; Bentham Science Publishers
• Subjects: Acetylcholine receptors; Adenosine receptors; Amine oxidase (flavin-containing); Animals; Antiparkinson Agents - chemistry; Antiparkinson Agents - therapeutic use; Autonomic nervous system; Cognitive ability; Drug Design; Drug development; Etiology; Humans; Mitochondria; Molecular Docking Simulation; Molecular Dynamics Simulation; Movement disorders; Neurodegenerative diseases; Oxidative stress; Parkinson Disease - drug therapy; Parkinson's disease; Sleep; Structure-activity relationships; acetylcholine receptors; and adenosine receptors; Parkinson's disease; QSAR; dopamine agonists; monoamine oxidase
• ISSN: 1570-159X; 1875-6190
• DOI: 10.2174/1570159X15666171128145423

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by debilitating motor deficits, as well as autonomic problems, cognitive declines, changes in affect and sleep disturbances. Although the scientific community has performed great efforts in the study of PD, and from the most diverse points of view, the disease remains incurable. The exact mechanism underlying its progression is unclear, but oxidative stress, mitochondrial dysfunction and inflammation are thought to play major roles in the etiology. Objective: Current pharmacological therapies for the treatment of Parkinson’s disease are mostly inadequate, and new therapeutic agents are much needed. Methods: In this review, recent advances in computer-aided drug design for the rational design of new compounds against Parkinson disease; using methods such as Quantitative Structure-Activity Relationships (QSAR), molecular docking, molecular dynamics and pharmacophore modeling are discussed. Results: In this review, four targets were selected: the enzyme monoamine oxidase, dopamine agonists, acetylcholine receptors, and adenosine receptors. Conclusion: Computer aided-drug design enables the creation of theoretical models that can be used in a large database to virtually screen for and identify novel candidate molecules.