Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action

Autores
da Silva, Juliana Pereira; Cristina da Silva Batista, Carin; Schumacher, Maria Lúcia; Rodríguez, Santiago; Talevi, Alan; Haddad, Paula; Castro, Guillermo Raul; Ferreira, Fabio Furlan
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Melphalan hydrochloride (MEH) is a chemotherapy drug with antitumor activity, recognized for its classification as an alkylating agent. Over the past few decades, the drug has been administered to patients undergoing treatment for breast and ovarian cancers, and it is also intended for the treatment of multiple myeloma. It is commercially available in tablet and injection forms; however, its oral administration presents some limitations, including presystemic elimination and incomplete absorption. This study employs a simulated annealing approach and powder X-ray diffraction data to determine its crystal structure. The structure is confirmed by Rietveld refinement, which reveals good visual agreement between the generated model and experimental data. Given that MEH has low solubility in water, a screening conducted in the Mercury program (utilizing the CSD-Materials module) indicates the potential use of various molecular synthons to enhance the drug’s efficacy. Grinding processes (manual and mechanochemical) are conducted with MEH and a coformer, caffeine (CAF), to form stoichiometric mixtures. The vibrational characteristics associated with MEH and CAF show low energy levels. The effects on cell viability of the MEH-CAF combination are studied at different concentrations and reveal more significant cytotoxicity against the HeLa cell line (cervical tumor) compared to healthy MRC-5 cells (human fetal lung fibroblasts).
Fil: da Silva, Juliana Pereira. Universidad Federal Do Abc; Brasil
Fil: Cristina da Silva Batista, Carin. Universidad Federal Do Abc; Brasil
Fil: Schumacher, Maria Lúcia. Universidade Federal de Sao Paulo.; Brasil
Fil: Rodríguez, Santiago. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Haddad, Paula. Universidad Federal Do Abc; Brasil
Fil: Castro, Guillermo Raul. Universidad Federal Do Abc; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferreira, Fabio Furlan. Universidad Federal Do Abc; Brasil
Materia
CANCER
CELLS
CRYSTAL STRUCTURE
FOURIER TRANSFORM INFRARED SPECTROSCOPY
PHARMACEUTICALS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/280626
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/280626
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic actionda Silva, Juliana PereiraCristina da Silva Batista, CarinSchumacher, Maria LúciaRodríguez, SantiagoTalevi, AlanHaddad, PaulaCastro, Guillermo RaulFerreira, Fabio FurlanCANCERCELLSCRYSTAL STRUCTUREFOURIER TRANSFORM INFRARED SPECTROSCOPYPHARMACEUTICALShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Melphalan hydrochloride (MEH) is a chemotherapy drug with antitumor activity, recognized for its classification as an alkylating agent. Over the past few decades, the drug has been administered to patients undergoing treatment for breast and ovarian cancers, and it is also intended for the treatment of multiple myeloma. It is commercially available in tablet and injection forms; however, its oral administration presents some limitations, including presystemic elimination and incomplete absorption. This study employs a simulated annealing approach and powder X-ray diffraction data to determine its crystal structure. The structure is confirmed by Rietveld refinement, which reveals good visual agreement between the generated model and experimental data. Given that MEH has low solubility in water, a screening conducted in the Mercury program (utilizing the CSD-Materials module) indicates the potential use of various molecular synthons to enhance the drug’s efficacy. Grinding processes (manual and mechanochemical) are conducted with MEH and a coformer, caffeine (CAF), to form stoichiometric mixtures. The vibrational characteristics associated with MEH and CAF show low energy levels. The effects on cell viability of the MEH-CAF combination are studied at different concentrations and reveal more significant cytotoxicity against the HeLa cell line (cervical tumor) compared to healthy MRC-5 cells (human fetal lung fibroblasts).Fil: da Silva, Juliana Pereira. Universidad Federal Do Abc; BrasilFil: Cristina da Silva Batista, Carin. Universidad Federal Do Abc; BrasilFil: Schumacher, Maria Lúcia. Universidade Federal de Sao Paulo.; BrasilFil: Rodríguez, Santiago. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Haddad, Paula. Universidad Federal Do Abc; BrasilFil: Castro, Guillermo Raul. Universidad Federal Do Abc; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferreira, Fabio Furlan. Universidad Federal Do Abc; BrasilAmerican Chemical Society2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/280626da Silva, Juliana Pereira; Cristina da Silva Batista, Carin; Schumacher, Maria Lúcia; Rodríguez, Santiago; Talevi, Alan; et al.; Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action; American Chemical Society; ACS Omega; 10; 20; 5-2025; 20661-206732470-13432470-1343CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsomega.5c01538info:eu-repo/semantics/altIdentifier/doi/10.1021/acsomega.5c01538info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:02:41Zoai:ri.conicet.gov.ar:11336/280626instacron: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:34982026-02-26 10:02:41.9CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
title Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
spellingShingle Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
da Silva, Juliana Pereira
CANCER
CELLS
CRYSTAL STRUCTURE
FOURIER TRANSFORM INFRARED SPECTROSCOPY
PHARMACEUTICALS
title_short Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
title_full Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
title_fullStr Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
title_full_unstemmed Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
title_sort Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action
dc.creator.none.fl_str_mv da Silva, Juliana Pereira
Cristina da Silva Batista, Carin
Schumacher, Maria Lúcia
Rodríguez, Santiago
Talevi, Alan
Haddad, Paula
Castro, Guillermo Raul
Ferreira, Fabio Furlan
author da Silva, Juliana Pereira
author_facet da Silva, Juliana Pereira
Cristina da Silva Batista, Carin
Schumacher, Maria Lúcia
Rodríguez, Santiago
Talevi, Alan
Haddad, Paula
Castro, Guillermo Raul
Ferreira, Fabio Furlan
author_role author
author2 Cristina da Silva Batista, Carin
Schumacher, Maria Lúcia
Rodríguez, Santiago
Talevi, Alan
Haddad, Paula
Castro, Guillermo Raul
Ferreira, Fabio Furlan
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CANCER
CELLS
CRYSTAL STRUCTURE
FOURIER TRANSFORM INFRARED SPECTROSCOPY
PHARMACEUTICALS
topic CANCER
CELLS
CRYSTAL STRUCTURE
FOURIER TRANSFORM INFRARED SPECTROSCOPY
PHARMACEUTICALS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Melphalan hydrochloride (MEH) is a chemotherapy drug with antitumor activity, recognized for its classification as an alkylating agent. Over the past few decades, the drug has been administered to patients undergoing treatment for breast and ovarian cancers, and it is also intended for the treatment of multiple myeloma. It is commercially available in tablet and injection forms; however, its oral administration presents some limitations, including presystemic elimination and incomplete absorption. This study employs a simulated annealing approach and powder X-ray diffraction data to determine its crystal structure. The structure is confirmed by Rietveld refinement, which reveals good visual agreement between the generated model and experimental data. Given that MEH has low solubility in water, a screening conducted in the Mercury program (utilizing the CSD-Materials module) indicates the potential use of various molecular synthons to enhance the drug’s efficacy. Grinding processes (manual and mechanochemical) are conducted with MEH and a coformer, caffeine (CAF), to form stoichiometric mixtures. The vibrational characteristics associated with MEH and CAF show low energy levels. The effects on cell viability of the MEH-CAF combination are studied at different concentrations and reveal more significant cytotoxicity against the HeLa cell line (cervical tumor) compared to healthy MRC-5 cells (human fetal lung fibroblasts).
Fil: da Silva, Juliana Pereira. Universidad Federal Do Abc; Brasil
Fil: Cristina da Silva Batista, Carin. Universidad Federal Do Abc; Brasil
Fil: Schumacher, Maria Lúcia. Universidade Federal de Sao Paulo.; Brasil
Fil: Rodríguez, Santiago. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Haddad, Paula. Universidad Federal Do Abc; Brasil
Fil: Castro, Guillermo Raul. Universidad Federal Do Abc; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferreira, Fabio Furlan. Universidad Federal Do Abc; Brasil
description Melphalan hydrochloride (MEH) is a chemotherapy drug with antitumor activity, recognized for its classification as an alkylating agent. Over the past few decades, the drug has been administered to patients undergoing treatment for breast and ovarian cancers, and it is also intended for the treatment of multiple myeloma. It is commercially available in tablet and injection forms; however, its oral administration presents some limitations, including presystemic elimination and incomplete absorption. This study employs a simulated annealing approach and powder X-ray diffraction data to determine its crystal structure. The structure is confirmed by Rietveld refinement, which reveals good visual agreement between the generated model and experimental data. Given that MEH has low solubility in water, a screening conducted in the Mercury program (utilizing the CSD-Materials module) indicates the potential use of various molecular synthons to enhance the drug’s efficacy. Grinding processes (manual and mechanochemical) are conducted with MEH and a coformer, caffeine (CAF), to form stoichiometric mixtures. The vibrational characteristics associated with MEH and CAF show low energy levels. The effects on cell viability of the MEH-CAF combination are studied at different concentrations and reveal more significant cytotoxicity against the HeLa cell line (cervical tumor) compared to healthy MRC-5 cells (human fetal lung fibroblasts).
publishDate 2025
dc.date.none.fl_str_mv 2025-05
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/11336/280626
da Silva, Juliana Pereira; Cristina da Silva Batista, Carin; Schumacher, Maria Lúcia; Rodríguez, Santiago; Talevi, Alan; et al.; Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action; American Chemical Society; ACS Omega; 10; 20; 5-2025; 20661-20673
2470-1343
2470-1343
CONICET Digital
CONICET
url http://hdl.handle.net/11336/280626
identifier_str_mv da Silva, Juliana Pereira; Cristina da Silva Batista, Carin; Schumacher, Maria Lúcia; Rodríguez, Santiago; Talevi, Alan; et al.; Crystal structure of melphalan hydrochloride and its association with caffeine improves its antineoplastic action; American Chemical Society; ACS Omega; 10; 20; 5-2025; 20661-20673
2470-1343
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://pubs.acs.org/doi/10.1021/acsomega.5c01538
info:eu-repo/semantics/altIdentifier/doi/10.1021/acsomega.5c01538
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 13.176822

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