Cheminformatics and virtual screening studies of COMT inhibitors as potential Parkinson’s disease therapeutics

Kalliopi Moschovou, Georgia Melagraki, Thomas Mavromoustakos, Lefteris C. Zacharia, Antreas Afantitis

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
JournalExpert Opinion on Drug Discovery
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Fingerprint

Parkinson Disease
Dopamine
Computer Simulation
Secondary Parkinson Disease
Therapeutics
Corpus Striatum
Catechol O-Methyltransferase
Nerve Degeneration
Dopaminergic Neurons
Central Nervous System Diseases
Expert Testimony
Levodopa
Hydroxyl Radical
Methylation
Biological Availability
Catecholamines

Keywords

  • Catechol-O-methyltransferase
  • cheminformatics
  • COMT inhibitors
  • drug design
  • Parkinson’s disease

Cite this

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abstract = "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.",
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Cheminformatics and virtual screening studies of COMT inhibitors as potential Parkinson’s disease therapeutics. / Moschovou, Kalliopi; Melagraki, Georgia; Mavromoustakos, Thomas; Zacharia, Lefteris C.; Afantitis, Antreas.

In: Expert Opinion on Drug Discovery, 01.01.2019.

Research output: Contribution to journalReview article

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