TY - JOUR
TI - Cheminformatics and virtual screening studies of COMT inhibitors as potential Parkinson’s disease therapeutics
AU - Moschovou, K.
AU - Melagraki, G.
AU - Mavromoustakos, T.
AU - Zacharia, L.C.
AU - Afantitis, A.
JO - Expert Opinion on Drug Discovery
PY - 2020
VL - 15
TODO - 1
SP - 53-62
PB - Taylor and Francis Ltd.
SN - 1746-0441, 1746-045X
TODO - 10.1080/17460441.2020.1691165
TODO - antiparkinson agent;  catechol methyltransferase inhibitor;  antiparkinson agent;  catechol methyltransferase inhibitor, binding affinity;  drug potency;  drug screening;  drug structure;  human;  Parkinson disease;  priority journal;  Review;  animal;  chemistry;  molecular dynamics;  Parkinson disease;  preclinical study;  procedures, Animals;  Antiparkinson Agents;  Catechol O-Methyltransferase Inhibitors;  Cheminformatics;  Drug Evaluation, Preclinical;  Molecular Dynamics Simulation;  Parkinson Disease
TODO - Introduction: Parkinson’s Disease (PD) is a neurodegenerative central nervous system (CNS) disorder characterized by dopaminergic neuron degeneration with consequent reduction in striatal dopamine (DA) levels that leads to motor symptoms. Catechol-O-methyltransferase (COMT, E.C 2.1.1.6) inactivates dopamine and other substrates bearing catechol through the methylation of a hydroxyl group. COMT inhibition can block metabolism of catecholamines including DA. Since the increase in DA bioavailability is dependent on the inhibition of DA metabolism at the periphery, the development of COMT inhibitors as adjuvants to levodopa/aromatic amino acid decarboxylase (AADC) inhibitor treatment improves the clinical benefits of PD symptomatic treatment significantly. Areas covered: This review focuses on the contribution of computational studies to develop novel COMT inhibitors as therapeutics of Parkinson’s disease with substantially improved efficacy. Expert opinion: The increasing use of in silico methods and the development of new chemoinformatic tools in combination with the knowledge gained from the development of different inhibitors studied both in silico, in vitro and in vivo, could help solve a number of issues related to the shortcomings of currently marketed treatments. They can also aid to open new avenues for centrally acting COMT inhibitors, and perhaps irreversible inhibitors, to be tested for PD and other neurological diseases. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
ER -