Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues

Detalhes bibliográficos
Autor(a) principal: da Silva, Suzane Rosa [UNESP]
Data de Publicação: 2022
Outros Autores: Kalaba, Predrag, Fabišiková, Anna, Zehl, Martin, Dragačević, Vladimir, dos Anjos, Luana Ribeiro [UNESP], Neill, Philip John, Wieder, Marcus, Prado-Roller, Alexander, Gajic, Natalie, Palaretti, Vinicius, da Silva, Gil Valdo Jose, Pifl, Christian, Lubec, Gert, Gonzalez, Eduardo R. Perez [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s00726-021-03106-4
http://hdl.handle.net/11449/222946
Resumo: Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R. Three compounds that showed the highest similarity index were selected for synthesis and bioactivity profiling. All main synthesis products as well as the isolated intermediates, were properly characterized. The physico-chemical analyses were performed using HRESIMS, GC/MS, LC/MS with UV–Vis detection, and FTIR, 1H NMR and 13C NMR spectroscopy. Binding to D1 and D2 receptors and inhibition of dopamine reuptake via dopamine transporter were measured for the synthesized analogues of DHX and SKF 38393.
id UNSP_9672bf1a9da0dbcc43690cccdf571a4f
oai_identifier_str oai:repositorio.unesp.br:11449/222946
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analoguesD1R agonistsD2R and DATDihydrexidineDopamine analogsSKF 38393Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R. Three compounds that showed the highest similarity index were selected for synthesis and bioactivity profiling. All main synthesis products as well as the isolated intermediates, were properly characterized. The physico-chemical analyses were performed using HRESIMS, GC/MS, LC/MS with UV–Vis detection, and FTIR, 1H NMR and 13C NMR spectroscopy. Binding to D1 and D2 receptors and inhibition of dopamine reuptake via dopamine transporter were measured for the synthesized analogues of DHX and SKF 38393.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratory of Fine Organic Chemistry Department of Chemistry and Biochemistry Faculty of Sciences and Technology of São Paulo State University, São PauloDepartment of Pharmaceutical Chemistry Faculty of Life Sciences University of Vienna, Althanstraße 14Mass Spectrometry Centre Faculty of Chemistry University of Vienna, Währinger Straße 38Department of Analytical Chemistry Faculty of Chemistry University of Vienna, Währinger Straße 38Centre for X-Ray Structure Analysis at Faculty of Chemistry University of Vienna, Währinger Straße 40-42Department of Chemistry Faculty of Philosophy Sciences and Letters of Ribeirão Preto University of São Paulo, Avenida dos Bandeirantes, 3900, SPDepartment of Molecular Neurosciences Centre for Brain Research Medical University of Vienna, Spitalgasse 4Department of Neuroproteomics Paracelsus Medical UniversityLaboratory of Fine Organic Chemistry Department of Chemistry and Biochemistry Faculty of Sciences and Technology of São Paulo State University, São PauloFAPESP: 2016/10149-0Universidade Estadual Paulista (UNESP)University of ViennaUniversidade de São Paulo (USP)Medical University of ViennaParacelsus Medical Universityda Silva, Suzane Rosa [UNESP]Kalaba, PredragFabišiková, AnnaZehl, MartinDragačević, Vladimirdos Anjos, Luana Ribeiro [UNESP]Neill, Philip JohnWieder, MarcusPrado-Roller, AlexanderGajic, NataliePalaretti, Viniciusda Silva, Gil Valdo JosePifl, ChristianLubec, GertGonzalez, Eduardo R. Perez [UNESP]2022-04-28T19:47:43Z2022-04-28T19:47:43Z2022-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article85-98http://dx.doi.org/10.1007/s00726-021-03106-4Amino Acids, v. 54, n. 1, p. 85-98, 2022.1438-21990939-4451http://hdl.handle.net/11449/22294610.1007/s00726-021-03106-42-s2.0-85120165074Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAmino Acidsinfo:eu-repo/semantics/openAccess2022-04-28T19:47:43Zoai:repositorio.unesp.br:11449/222946Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:22:50.692547Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
title Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
spellingShingle Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
da Silva, Suzane Rosa [UNESP]
D1R agonists
D2R and DAT
Dihydrexidine
Dopamine analogs
SKF 38393
title_short Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
title_full Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
title_fullStr Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
title_full_unstemmed Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
title_sort Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues
author da Silva, Suzane Rosa [UNESP]
author_facet da Silva, Suzane Rosa [UNESP]
Kalaba, Predrag
Fabišiková, Anna
Zehl, Martin
Dragačević, Vladimir
dos Anjos, Luana Ribeiro [UNESP]
Neill, Philip John
Wieder, Marcus
Prado-Roller, Alexander
Gajic, Natalie
Palaretti, Vinicius
da Silva, Gil Valdo Jose
Pifl, Christian
Lubec, Gert
Gonzalez, Eduardo R. Perez [UNESP]
author_role author
author2 Kalaba, Predrag
Fabišiková, Anna
Zehl, Martin
Dragačević, Vladimir
dos Anjos, Luana Ribeiro [UNESP]
Neill, Philip John
Wieder, Marcus
Prado-Roller, Alexander
Gajic, Natalie
Palaretti, Vinicius
da Silva, Gil Valdo Jose
Pifl, Christian
Lubec, Gert
Gonzalez, Eduardo R. Perez [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
University of Vienna
Universidade de São Paulo (USP)
Medical University of Vienna
Paracelsus Medical University
dc.contributor.author.fl_str_mv da Silva, Suzane Rosa [UNESP]
Kalaba, Predrag
Fabišiková, Anna
Zehl, Martin
Dragačević, Vladimir
dos Anjos, Luana Ribeiro [UNESP]
Neill, Philip John
Wieder, Marcus
Prado-Roller, Alexander
Gajic, Natalie
Palaretti, Vinicius
da Silva, Gil Valdo Jose
Pifl, Christian
Lubec, Gert
Gonzalez, Eduardo R. Perez [UNESP]
dc.subject.por.fl_str_mv D1R agonists
D2R and DAT
Dihydrexidine
Dopamine analogs
SKF 38393
topic D1R agonists
D2R and DAT
Dihydrexidine
Dopamine analogs
SKF 38393
description Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R. Three compounds that showed the highest similarity index were selected for synthesis and bioactivity profiling. All main synthesis products as well as the isolated intermediates, were properly characterized. The physico-chemical analyses were performed using HRESIMS, GC/MS, LC/MS with UV–Vis detection, and FTIR, 1H NMR and 13C NMR spectroscopy. Binding to D1 and D2 receptors and inhibition of dopamine reuptake via dopamine transporter were measured for the synthesized analogues of DHX and SKF 38393.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-28T19:47:43Z
2022-04-28T19:47:43Z
2022-01-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1007/s00726-021-03106-4
Amino Acids, v. 54, n. 1, p. 85-98, 2022.
1438-2199
0939-4451
http://hdl.handle.net/11449/222946
10.1007/s00726-021-03106-4
2-s2.0-85120165074
url http://dx.doi.org/10.1007/s00726-021-03106-4
http://hdl.handle.net/11449/222946
identifier_str_mv Amino Acids, v. 54, n. 1, p. 85-98, 2022.
1438-2199
0939-4451
10.1007/s00726-021-03106-4
2-s2.0-85120165074
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Amino Acids
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 85-98
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128506145538048