Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide

Autores
Bruno, Flavia Paola; Caira, Mino R.; Monti, Gustavo Alberto; Kassuha, Diego Enrique; Sperandeo, Norma Rebeca
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug– enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna21 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å3 , Z = 8, Dx = 1.629 g cm3 , R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.
Fil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Caira, Mino R.. University of Cape Town; Sudáfrica
Fil: Monti, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina
Fil: Kassuha, Diego Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Materia
CRYSTAL STRUCTURE
DRIFT AND FTIR
NITAZOXANIDE
SOLID AND SOLUTION NMR
THERMAL ANALYSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/187802
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/187802
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanideBruno, Flavia PaolaCaira, Mino R.Monti, Gustavo AlbertoKassuha, Diego EnriqueSperandeo, Norma RebecaCRYSTAL STRUCTUREDRIFT AND FTIRNITAZOXANIDESOLID AND SOLUTION NMRTHERMAL ANALYSIShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug– enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna21 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å3 , Z = 8, Dx = 1.629 g cm3 , R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.Fil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Caira, Mino R.. University of Cape Town; SudáfricaFil: Monti, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Kassuha, Diego Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaElsevier Science2010-12-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/187802Bruno, Flavia Paola; Caira, Mino R.; Monti, Gustavo Alberto; Kassuha, Diego Enrique; Sperandeo, Norma Rebeca; Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide; Elsevier Science; Journal of Molecular Structure; 984; 1-3; 15-12-2010; 51-570022-28601872-8014CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022286010007416info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molstruc.2010.09.006info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:20:39Zoai:ri.conicet.gov.ar:11336/187802instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:20:39.765CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
title Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
spellingShingle Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
Bruno, Flavia Paola
CRYSTAL STRUCTURE
DRIFT AND FTIR
NITAZOXANIDE
SOLID AND SOLUTION NMR
THERMAL ANALYSIS
title_short Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
title_full Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
title_fullStr Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
title_full_unstemmed Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
title_sort Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide
dc.creator.none.fl_str_mv Bruno, Flavia Paola
Caira, Mino R.
Monti, Gustavo Alberto
Kassuha, Diego Enrique
Sperandeo, Norma Rebeca
author Bruno, Flavia Paola
author_facet Bruno, Flavia Paola
Caira, Mino R.
Monti, Gustavo Alberto
Kassuha, Diego Enrique
Sperandeo, Norma Rebeca
author_role author
author2 Caira, Mino R.
Monti, Gustavo Alberto
Kassuha, Diego Enrique
Sperandeo, Norma Rebeca
author2_role author
author
author
author
dc.subject.none.fl_str_mv CRYSTAL STRUCTURE
DRIFT AND FTIR
NITAZOXANIDE
SOLID AND SOLUTION NMR
THERMAL ANALYSIS
topic CRYSTAL STRUCTURE
DRIFT AND FTIR
NITAZOXANIDE
SOLID AND SOLUTION NMR
THERMAL ANALYSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug– enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna21 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å3 , Z = 8, Dx = 1.629 g cm3 , R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.
Fil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Caira, Mino R.. University of Cape Town; Sudáfrica
Fil: Monti, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina
Fil: Kassuha, Diego Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
description Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug– enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna21 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å3 , Z = 8, Dx = 1.629 g cm3 , R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.
publishDate 2010
dc.date.none.fl_str_mv 2010-12-15
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/187802
Bruno, Flavia Paola; Caira, Mino R.; Monti, Gustavo Alberto; Kassuha, Diego Enrique; Sperandeo, Norma Rebeca; Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide; Elsevier Science; Journal of Molecular Structure; 984; 1-3; 15-12-2010; 51-57
0022-2860
1872-8014
CONICET Digital
CONICET
url http://hdl.handle.net/11336/187802
identifier_str_mv Bruno, Flavia Paola; Caira, Mino R.; Monti, Gustavo Alberto; Kassuha, Diego Enrique; Sperandeo, Norma Rebeca; Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide; Elsevier Science; Journal of Molecular Structure; 984; 1-3; 15-12-2010; 51-57
0022-2860
1872-8014
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022286010007416
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molstruc.2010.09.006
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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