Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles

Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles

New <i>N</i>-acetyl/<i>N</i>-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enan...

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Main Authors: Paolo Guglielmi, Simone Carradori, Giulio Poli, Daniela Secci, Roberto Cirilli, Giulia Rotondi, Paola Chimenti, Anél Petzer, Jacobus P. Petzer
Format: Article
Language:English
Published: MDPI AG 2019-01-01
Series:Molecules
Subjects:
pyrazoline
monoamine oxidase
enantioseparation
molecular modelling
prenyl
Online Access:https://www.mdpi.com/1420-3049/24/3/484
id doaj-4454e3dbe88d4979a5ac2e720f57987b
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spelling doaj-4454e3dbe88d4979a5ac2e720f57987b2020-11-24T21:48:33ZengMDPI AGMolecules1420-30492019-01-0124348410.3390/molecules24030484molecules24030484Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazolesPaolo Guglielmi0Simone Carradori1Giulio Poli2Daniela Secci3Roberto Cirilli4Giulia Rotondi5Paola Chimenti6Anél Petzer7Jacobus P. Petzer8Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDepartment of Pharmacy, “G. D’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università di Pisa, via Bonanno 6, 56126 Pisa, ItalyDipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyCentro nazionale per il controllo e la valutazione dei farmaci, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyPharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South AfricaPharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South AfricaNew <i>N</i>-acetyl/<i>N</i>-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. <i>p</i>-Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases.https://www.mdpi.com/1420-3049/24/3/484pyrazolinemonoamine oxidaseenantioseparationmolecular modellingprenyl
collection DOAJ
language English
format Article
sources DOAJ
author Paolo Guglielmi
Simone Carradori
Giulio Poli
Daniela Secci
Roberto Cirilli
Giulia Rotondi
Paola Chimenti
Anél Petzer
Jacobus P. Petzer
spellingShingle Paolo Guglielmi
Simone Carradori
Giulio Poli
Daniela Secci
Roberto Cirilli
Giulia Rotondi
Paola Chimenti
Anél Petzer
Jacobus P. Petzer
Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles
Molecules
pyrazoline
monoamine oxidase
enantioseparation
molecular modelling
prenyl
author_facet Paolo Guglielmi
Simone Carradori
Giulio Poli
Daniela Secci
Roberto Cirilli
Giulia Rotondi
Paola Chimenti
Anél Petzer
Jacobus P. Petzer
author_sort Paolo Guglielmi
title Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles
title_short Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles
title_full Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles
title_fullStr Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles
title_full_unstemmed Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazoles
title_sort design, synthesis, docking studies and monoamine oxidase inhibition of a small library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1<i>h</i>)-pyrazoles
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2019-01-01
description New <i>N</i>-acetyl/<i>N</i>-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. <i>p</i>-Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases.
topic pyrazoline
monoamine oxidase
enantioseparation
molecular modelling
prenyl
url https://www.mdpi.com/1420-3049/24/3/484
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