Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1039/d1ra01066b http://hdl.handle.net/11449/208707 |
Resumo: | NADPH oxidases are pharmacological targets for the treatment of inflammation-based diseases. This work presents the synthesis and study of a caffeic acid/phthalimide hybrid compound (C2) as a potential inhibitor of NADPH oxidases. Throughout the study, we have compared compound C2 with its precursor caffeic acid (C1). The redox properties were compared using three different antioxidant methodologies and showed that C2 was slightly less effective than C1, a well-established and robust antioxidant. However, C2 was three-fold more effective than albumin (used as a model protein). This chemical feature was decisive for the higher efficiency of C2 as an inhibitor of the release of superoxide anions by stimulated neutrophils and enzymatic activity of cell-free NADPH oxidase. Docking simulation studies were performed using the crystal structure of the recombinant dehydrogenase domain of the isoform NOX5 of C. stagnale, which retains the FAD cofactor (PDB: 5O0X). Considering that C2 could bind at the FAD redox site of NOX5, studies were conducted by comparing the interactions and binding energies of C1 and C2. The binding energies were -50.30 (C1) and -74.88 (C2) (kJ mol-1), which is in agreement with the higher efficacy of the latter as an NADPH oxidase inhibitor. In conclusion, incorporating the phthalimide moiety into caffeic acid was decisive for its effectiveness as an NADPH oxidase inhibitor. |
id |
UNSP_b5842800fda34334e4ac404bb1771cd3 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/208707 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibitionNADPH oxidases are pharmacological targets for the treatment of inflammation-based diseases. This work presents the synthesis and study of a caffeic acid/phthalimide hybrid compound (C2) as a potential inhibitor of NADPH oxidases. Throughout the study, we have compared compound C2 with its precursor caffeic acid (C1). The redox properties were compared using three different antioxidant methodologies and showed that C2 was slightly less effective than C1, a well-established and robust antioxidant. However, C2 was three-fold more effective than albumin (used as a model protein). This chemical feature was decisive for the higher efficiency of C2 as an inhibitor of the release of superoxide anions by stimulated neutrophils and enzymatic activity of cell-free NADPH oxidase. Docking simulation studies were performed using the crystal structure of the recombinant dehydrogenase domain of the isoform NOX5 of C. stagnale, which retains the FAD cofactor (PDB: 5O0X). Considering that C2 could bind at the FAD redox site of NOX5, studies were conducted by comparing the interactions and binding energies of C1 and C2. The binding energies were -50.30 (C1) and -74.88 (C2) (kJ mol-1), which is in agreement with the higher efficacy of the latter as an NADPH oxidase inhibitor. In conclusion, incorporating the phthalimide moiety into caffeic acid was decisive for its effectiveness as an NADPH oxidase inhibitor.Department of Chemistry Faculty of Sciences UNESP-São Paulo State UniversityDepartment of Pharmaceutical Sciences Maringa State University (UEM)Department of Chemistry Faculty of Sciences UNESP-São Paulo State UniversityUniversidade Estadual Paulista (Unesp)Universidade Estadual de Maringá (UEM)Santos, Willian Henrique dos [UNESP]Yoguim, Maurício Ikeda [UNESP]Daré, Regina GomesDa Silva-Filho, Luiz Carlos [UNESP]Lautenschlager, Sueli Oliveira SilvaXimenes, Valdecir Farias [UNESP]2021-06-25T11:17:45Z2021-06-25T11:17:45Z2021-05-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17880-17890http://dx.doi.org/10.1039/d1ra01066bRSC Advances, v. 11, n. 29, p. 17880-17890, 2021.2046-2069http://hdl.handle.net/11449/20870710.1039/d1ra01066b2-s2.0-85106406301Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengRSC Advancesinfo:eu-repo/semantics/openAccess2024-04-29T18:17:12Zoai:repositorio.unesp.br:11449/208707Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-04-29T18:17:12Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
title |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
spellingShingle |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition Santos, Willian Henrique dos [UNESP] |
title_short |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
title_full |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
title_fullStr |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
title_full_unstemmed |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
title_sort |
Development of a caffeic acid-phthalimide hybrid compound for NADPH oxidase inhibition |
author |
Santos, Willian Henrique dos [UNESP] |
author_facet |
Santos, Willian Henrique dos [UNESP] Yoguim, Maurício Ikeda [UNESP] Daré, Regina Gomes Da Silva-Filho, Luiz Carlos [UNESP] Lautenschlager, Sueli Oliveira Silva Ximenes, Valdecir Farias [UNESP] |
author_role |
author |
author2 |
Yoguim, Maurício Ikeda [UNESP] Daré, Regina Gomes Da Silva-Filho, Luiz Carlos [UNESP] Lautenschlager, Sueli Oliveira Silva Ximenes, Valdecir Farias [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Estadual de Maringá (UEM) |
dc.contributor.author.fl_str_mv |
Santos, Willian Henrique dos [UNESP] Yoguim, Maurício Ikeda [UNESP] Daré, Regina Gomes Da Silva-Filho, Luiz Carlos [UNESP] Lautenschlager, Sueli Oliveira Silva Ximenes, Valdecir Farias [UNESP] |
description |
NADPH oxidases are pharmacological targets for the treatment of inflammation-based diseases. This work presents the synthesis and study of a caffeic acid/phthalimide hybrid compound (C2) as a potential inhibitor of NADPH oxidases. Throughout the study, we have compared compound C2 with its precursor caffeic acid (C1). The redox properties were compared using three different antioxidant methodologies and showed that C2 was slightly less effective than C1, a well-established and robust antioxidant. However, C2 was three-fold more effective than albumin (used as a model protein). This chemical feature was decisive for the higher efficiency of C2 as an inhibitor of the release of superoxide anions by stimulated neutrophils and enzymatic activity of cell-free NADPH oxidase. Docking simulation studies were performed using the crystal structure of the recombinant dehydrogenase domain of the isoform NOX5 of C. stagnale, which retains the FAD cofactor (PDB: 5O0X). Considering that C2 could bind at the FAD redox site of NOX5, studies were conducted by comparing the interactions and binding energies of C1 and C2. The binding energies were -50.30 (C1) and -74.88 (C2) (kJ mol-1), which is in agreement with the higher efficacy of the latter as an NADPH oxidase inhibitor. In conclusion, incorporating the phthalimide moiety into caffeic acid was decisive for its effectiveness as an NADPH oxidase inhibitor. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T11:17:45Z 2021-06-25T11:17:45Z 2021-05-12 |
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/10.1039/d1ra01066b RSC Advances, v. 11, n. 29, p. 17880-17890, 2021. 2046-2069 http://hdl.handle.net/11449/208707 10.1039/d1ra01066b 2-s2.0-85106406301 |
url |
http://dx.doi.org/10.1039/d1ra01066b http://hdl.handle.net/11449/208707 |
identifier_str_mv |
RSC Advances, v. 11, n. 29, p. 17880-17890, 2021. 2046-2069 10.1039/d1ra01066b 2-s2.0-85106406301 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
RSC Advances |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
17880-17890 |
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_ |
1803047039454412800 |