Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.molstruc.2022.133888 http://hdl.handle.net/11449/242155 |
Resumo: | In this work, two palladium(II) complexes, namely, [Pd(L1)2(phen)] 1 and [Pd(L2)2(phen)] 2 (L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and phen = 1,10-phenanthroline), were prepared and charactherized by conventional techniques. In both complexes, the spectral data indicated that L1 and L2 are coordinated to the metal in a monodentate manner through the sulfur atom (S−), while a phenanthroline molecule acting as a bidentate ligand completes the coordination sphere. This proposal was supported by DFT calculation of structures and NMR spectra. Subsequently, the free ligands and their metal complexes were tested in vitro against the human prostate cell lines PNT-2 (non-tumorigenic), LNCaP (androgen-sensitive prostate cancer) and PC-3 (castration-resistant prostate cancer), as well as in two human breast cancer cell lines, MCF7 (luminal) and MDA-MB231 (triple-negative). Regarding cytotoxicity, all compounds were considered inactive, since the IC50 values found were higher than 80 µM. The complexes were also evaluated for activity against Mycobacterium tuberculosis, and 1 showed good activity (MIC = 8.94 µg/mL), while 2 exhibited moderate to poor activity (MIC > 25.0 µg/mL), revealing that an increase in the aliphatic chain makes it less active. A conformation sampling was conducted for the complexes 1 and 2 using molecular dynamics simulation. The analysis provided a clear picture of the steric and electrostatic flexibility of these compounds, which is an important feature for multi-target drugs. |
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Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives1,3,4-oxadiazole-2-(3H)-thione, DFTCytotoxicityMycobacterium tuberculosisPalladium complexesTuberculosisIn this work, two palladium(II) complexes, namely, [Pd(L1)2(phen)] 1 and [Pd(L2)2(phen)] 2 (L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and phen = 1,10-phenanthroline), were prepared and charactherized by conventional techniques. In both complexes, the spectral data indicated that L1 and L2 are coordinated to the metal in a monodentate manner through the sulfur atom (S−), while a phenanthroline molecule acting as a bidentate ligand completes the coordination sphere. This proposal was supported by DFT calculation of structures and NMR spectra. Subsequently, the free ligands and their metal complexes were tested in vitro against the human prostate cell lines PNT-2 (non-tumorigenic), LNCaP (androgen-sensitive prostate cancer) and PC-3 (castration-resistant prostate cancer), as well as in two human breast cancer cell lines, MCF7 (luminal) and MDA-MB231 (triple-negative). Regarding cytotoxicity, all compounds were considered inactive, since the IC50 values found were higher than 80 µM. The complexes were also evaluated for activity against Mycobacterium tuberculosis, and 1 showed good activity (MIC = 8.94 µg/mL), while 2 exhibited moderate to poor activity (MIC > 25.0 µg/mL), revealing that an increase in the aliphatic chain makes it less active. A conformation sampling was conducted for the complexes 1 and 2 using molecular dynamics simulation. The analysis provided a clear picture of the steric and electrostatic flexibility of these compounds, which is an important feature for multi-target drugs.Instituto de Química Universidade Federal de Uberlândia, Av. João Naves de Ávila, 2121, Campus Santa MônicaInstituto Ciências Exatas e da Terra Universidade Federal de Mato Grosso, MTFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista, Campus AraraquaraDepartamento de Química Universidade Federal de Juiz de Fora, Campus MartelosInstituto de Biotecnologia Universidade Federal de Uberlândia, MGFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista, Campus AraraquaraUniversidade Federal de Uberlândia (UFU)Universidade Federal de Mato GrossoUniversidade Estadual Paulista (UNESP)Universidade Federal de Juiz de ForaSouza, Wesley AlmeidaDemarqui, Fernanda Manaia [UNESP]de Almeida, Angelina MariaSilva, Raphael Tristão CruvinelAlves, Douglas AlexsanderAraújo, Thaise GonçalvesResende, Jackson Antonio Lamounier CamargosPavan, Fernando Rogério [UNESP]Santos, Hélio Ferreira Dosde Almeida, Mauro VieiraGuerra, Wendell2023-03-02T10:25:47Z2023-03-02T10:25:47Z2022-12-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.molstruc.2022.133888Journal of Molecular Structure, v. 1270.0022-2860http://hdl.handle.net/11449/24215510.1016/j.molstruc.2022.1338882-s2.0-85136096856Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Molecular Structureinfo:eu-repo/semantics/openAccess2023-03-02T10:25:48Zoai:repositorio.unesp.br:11449/242155Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-03-02T10:25:48Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
title |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
spellingShingle |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives Souza, Wesley Almeida 1,3,4-oxadiazole-2-(3H)-thione, DFT Cytotoxicity Mycobacterium tuberculosis Palladium complexes Tuberculosis |
title_short |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
title_full |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
title_fullStr |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
title_full_unstemmed |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
title_sort |
Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives |
author |
Souza, Wesley Almeida |
author_facet |
Souza, Wesley Almeida Demarqui, Fernanda Manaia [UNESP] de Almeida, Angelina Maria Silva, Raphael Tristão Cruvinel Alves, Douglas Alexsander Araújo, Thaise Gonçalves Resende, Jackson Antonio Lamounier Camargos Pavan, Fernando Rogério [UNESP] Santos, Hélio Ferreira Dos de Almeida, Mauro Vieira Guerra, Wendell |
author_role |
author |
author2 |
Demarqui, Fernanda Manaia [UNESP] de Almeida, Angelina Maria Silva, Raphael Tristão Cruvinel Alves, Douglas Alexsander Araújo, Thaise Gonçalves Resende, Jackson Antonio Lamounier Camargos Pavan, Fernando Rogério [UNESP] Santos, Hélio Ferreira Dos de Almeida, Mauro Vieira Guerra, Wendell |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Uberlândia (UFU) Universidade Federal de Mato Grosso Universidade Estadual Paulista (UNESP) Universidade Federal de Juiz de Fora |
dc.contributor.author.fl_str_mv |
Souza, Wesley Almeida Demarqui, Fernanda Manaia [UNESP] de Almeida, Angelina Maria Silva, Raphael Tristão Cruvinel Alves, Douglas Alexsander Araújo, Thaise Gonçalves Resende, Jackson Antonio Lamounier Camargos Pavan, Fernando Rogério [UNESP] Santos, Hélio Ferreira Dos de Almeida, Mauro Vieira Guerra, Wendell |
dc.subject.por.fl_str_mv |
1,3,4-oxadiazole-2-(3H)-thione, DFT Cytotoxicity Mycobacterium tuberculosis Palladium complexes Tuberculosis |
topic |
1,3,4-oxadiazole-2-(3H)-thione, DFT Cytotoxicity Mycobacterium tuberculosis Palladium complexes Tuberculosis |
description |
In this work, two palladium(II) complexes, namely, [Pd(L1)2(phen)] 1 and [Pd(L2)2(phen)] 2 (L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and phen = 1,10-phenanthroline), were prepared and charactherized by conventional techniques. In both complexes, the spectral data indicated that L1 and L2 are coordinated to the metal in a monodentate manner through the sulfur atom (S−), while a phenanthroline molecule acting as a bidentate ligand completes the coordination sphere. This proposal was supported by DFT calculation of structures and NMR spectra. Subsequently, the free ligands and their metal complexes were tested in vitro against the human prostate cell lines PNT-2 (non-tumorigenic), LNCaP (androgen-sensitive prostate cancer) and PC-3 (castration-resistant prostate cancer), as well as in two human breast cancer cell lines, MCF7 (luminal) and MDA-MB231 (triple-negative). Regarding cytotoxicity, all compounds were considered inactive, since the IC50 values found were higher than 80 µM. The complexes were also evaluated for activity against Mycobacterium tuberculosis, and 1 showed good activity (MIC = 8.94 µg/mL), while 2 exhibited moderate to poor activity (MIC > 25.0 µg/mL), revealing that an increase in the aliphatic chain makes it less active. A conformation sampling was conducted for the complexes 1 and 2 using molecular dynamics simulation. The analysis provided a clear picture of the steric and electrostatic flexibility of these compounds, which is an important feature for multi-target drugs. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-15 2023-03-02T10:25:47Z 2023-03-02T10:25:47Z |
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/10.1016/j.molstruc.2022.133888 Journal of Molecular Structure, v. 1270. 0022-2860 http://hdl.handle.net/11449/242155 10.1016/j.molstruc.2022.133888 2-s2.0-85136096856 |
url |
http://dx.doi.org/10.1016/j.molstruc.2022.133888 http://hdl.handle.net/11449/242155 |
identifier_str_mv |
Journal of Molecular Structure, v. 1270. 0022-2860 10.1016/j.molstruc.2022.133888 2-s2.0-85136096856 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Molecular Structure |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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_ |
1792962315413356545 |