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dc.contributor.authorRodríguez-Enríquez F.
dc.contributor.authorViña D.
dc.contributor.authorUriarte E.
dc.contributor.authorFontenla J.A.
dc.contributor.authorMatos M.J.
dc.date.accessioned2020-09-02T22:27:06Z
dc.date.available2020-09-02T22:27:06Z
dc.date.issued2020
dc.identifier10.1016/j.bioorg.2020.103986
dc.identifier.citation101, , -
dc.identifier.issn00452068
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6054
dc.descriptionMonoamine oxidase B (MAO-B) inhibitors are still receiving great attention as promising therapeutic agents for central nervous system disorders. This study explores, for the first time, the potential of 3-thiophenylcoumarins as in vitro and in vivo agents against Parkinsońs disease. Twelve compounds were synthesized via Perkin-Oglialoro reaction, and in vitro evaluation of six hydroxylated molecules was performed. MAO-A and MAO-B inhibition, DPPH scavenging and inhibition of ROS formation, neurotoxicity on motor cortex neurons and neuroprotection against H2O2, were studied. In vivo effect on locomotor activity using the open field test was also evaluated for the best candidate [3-(4′-bromothiophen-2′-yl)-7-hydroxycoumarin, 5], a potent, selective and reversible MAO-B inhibitor (IC50 = 140 nM). This compound proved to have a slightly better in vivo profile than selegiline, one of the currently treatments for Parkinson's disease, in reserpinized mice pretreated with levodopa and benserazide. Results suggested that, comparing positions 7 and 8, substitution at position 7 of the coumarin scaffold is better for the enzymatic inhibition. However, the presence of a catechol at positions 7 and 8 exponentially increases the antioxidant potential and the neuroprotective properties. Finally, all the molecules present good theoretical physicochemical properties that make them excellent candidates for the optimization of a lead compound. © 2020 Elsevier Inc.
dc.language.isoen
dc.publisherAcademic Press Inc.
dc.subject3-Thiophenylcoumarins
dc.subjectDPPH scavengers
dc.subjectmonoamine oxidase B inhibitors
dc.subjectNeuroprotectors
dc.subjectOpen field test
dc.subjectParkinson's disease
dc.subject3 (4' bromothiophen 2' yl) 7 hydroxycoumarin
dc.subject3 (4' bromothiophen 2' yl) 7,8 dihydroxycoumarin
dc.subject3 (4' bromothiophen 2' yl) 8 hydroxycoumarin
dc.subject3 thiophenylcoumarin derivative
dc.subject7 hydroxy 3 (thiophen 3' yl)coumarin
dc.subject7,8 dihydroxy 3 (thiophen 3' yl)coumarin
dc.subject8 hydroxy 3 (thiophen 3' yl)coumarin
dc.subjectamine oxidase (flavin containing) isoenzyme A
dc.subjectamine oxidase (flavin containing) isoenzyme B
dc.subjectcoumarin derivative
dc.subjecthydrogen peroxide
dc.subjectlevodopa
dc.subjectselegiline
dc.subjectunclassified drug
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectantioxidant activity
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectDPPH radical scavenging assay
dc.subjectdrug potency
dc.subjectdrug selectivity
dc.subjectdrug synthesis
dc.subjectembryo
dc.subjectenzyme inhibition
dc.subjectfemale
dc.subjectIC50
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectlocomotion
dc.subjectmale
dc.subjectmotor cortex
dc.subjectmouse
dc.subjectneuroprotection
dc.subjectneurotoxicity
dc.subjectnonhuman
dc.subjectopen field test
dc.subjectParkinson disease
dc.subjectpriority journal
dc.subjectrat
dc.subjectstructure activity relation
dc.titleDiscovery and optimization of 3-thiophenylcoumarins as novel agents against Parkinson's disease: Synthesis, in vitro and in vivo studies
dc.typeArticle


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