Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi

Autores
Raviolo, Mónica Ana; Solana, M. E.; Novoa, M. M.; Gualdesi, María Soledad; Alba Soto, Catalina Dirney; Briñon. M. C.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is caused by Trypanosoma cruzi (T. cruzi) leading to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available using drugs such as benznidazole and nifurtimox. Here, C6-alkyl(2aec) and N1-acyl (3aec) derivatives of Allopurinol (Allop, compound with activity against T. cruzi) were synthesized in good yields and their structures were unambiguously characterized. Only 2a, 2b and 3c showed inhibitory activity against the proliferative stages of the parasite when tested at 1 mg mL1 with the 3c derivative exhibiting an IC50 value similar to that of Allop and not being toxic for mammalian cells. Relevant pharmaceutical physicochemical properties (pKa, stability, solubility, lipophilicity) were also determined as well by using Lipinski?s rule, polar surface area and molecular rigidity. Taken together, the results demonstrated that the studied derivatives had optimal properties for bioavailability and oral absorption. For the stability studies, Micellar Liquid Chromatography was used as the analytical method which was fully validated according to the FDA guidelines and shown to be a suitable, sensitive and simple method for routine analysis of these Allop derivatives.
Fil: Raviolo, Mónica Ana. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina
Fil: Solana, M. E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Novoa, M. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Gualdesi, María Soledad. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina
Fil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Briñon. M. C.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina
Materia
Allopurinol Derivatives
Physicochemical Properties
Trypanocidal Activity
Trypanosoma Cruzi
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:11336/8511
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/8511
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruziRaviolo, Mónica AnaSolana, M. E.Novoa, M. M.Gualdesi, María SoledadAlba Soto, Catalina DirneyBriñon. M. C.Allopurinol DerivativesPhysicochemical PropertiesTrypanocidal ActivityTrypanosoma Cruzihttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Chagas disease is caused by Trypanosoma cruzi (T. cruzi) leading to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available using drugs such as benznidazole and nifurtimox. Here, C6-alkyl(2aec) and N1-acyl (3aec) derivatives of Allopurinol (Allop, compound with activity against T. cruzi) were synthesized in good yields and their structures were unambiguously characterized. Only 2a, 2b and 3c showed inhibitory activity against the proliferative stages of the parasite when tested at 1 mg mL1 with the 3c derivative exhibiting an IC50 value similar to that of Allop and not being toxic for mammalian cells. Relevant pharmaceutical physicochemical properties (pKa, stability, solubility, lipophilicity) were also determined as well by using Lipinski?s rule, polar surface area and molecular rigidity. Taken together, the results demonstrated that the studied derivatives had optimal properties for bioavailability and oral absorption. For the stability studies, Micellar Liquid Chromatography was used as the analytical method which was fully validated according to the FDA guidelines and shown to be a suitable, sensitive and simple method for routine analysis of these Allop derivatives.Fil: Raviolo, Mónica Ana. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; ArgentinaFil: Solana, M. E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaFil: Novoa, M. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaFil: Gualdesi, María Soledad. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; ArgentinaFil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaFil: Briñon. M. C.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; ArgentinaElsevier Masson2013-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8511Raviolo, Mónica Ana; Solana, M. E.; Novoa, M. M.; Gualdesi, María Soledad; Alba Soto, Catalina Dirney; et al.; Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi; Elsevier Masson; European Journal Of Medical Chemistry; 69; 8-2013; 455-4640223-5234enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523413005631info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2013.08.045info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:16:37Zoai:ri.conicet.gov.ar:11336/8511instacron: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:34982025-09-17 11:16:37.76CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
title Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
spellingShingle Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
Raviolo, Mónica Ana
Allopurinol Derivatives
Physicochemical Properties
Trypanocidal Activity
Trypanosoma Cruzi
title_short Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
title_full Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
title_fullStr Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
title_full_unstemmed Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
title_sort Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi
dc.creator.none.fl_str_mv Raviolo, Mónica Ana
Solana, M. E.
Novoa, M. M.
Gualdesi, María Soledad
Alba Soto, Catalina Dirney
Briñon. M. C.
author Raviolo, Mónica Ana
author_facet Raviolo, Mónica Ana
Solana, M. E.
Novoa, M. M.
Gualdesi, María Soledad
Alba Soto, Catalina Dirney
Briñon. M. C.
author_role author
author2 Solana, M. E.
Novoa, M. M.
Gualdesi, María Soledad
Alba Soto, Catalina Dirney
Briñon. M. C.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Allopurinol Derivatives
Physicochemical Properties
Trypanocidal Activity
Trypanosoma Cruzi
topic Allopurinol Derivatives
Physicochemical Properties
Trypanocidal Activity
Trypanosoma Cruzi
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease is caused by Trypanosoma cruzi (T. cruzi) leading to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available using drugs such as benznidazole and nifurtimox. Here, C6-alkyl(2aec) and N1-acyl (3aec) derivatives of Allopurinol (Allop, compound with activity against T. cruzi) were synthesized in good yields and their structures were unambiguously characterized. Only 2a, 2b and 3c showed inhibitory activity against the proliferative stages of the parasite when tested at 1 mg mL1 with the 3c derivative exhibiting an IC50 value similar to that of Allop and not being toxic for mammalian cells. Relevant pharmaceutical physicochemical properties (pKa, stability, solubility, lipophilicity) were also determined as well by using Lipinski?s rule, polar surface area and molecular rigidity. Taken together, the results demonstrated that the studied derivatives had optimal properties for bioavailability and oral absorption. For the stability studies, Micellar Liquid Chromatography was used as the analytical method which was fully validated according to the FDA guidelines and shown to be a suitable, sensitive and simple method for routine analysis of these Allop derivatives.
Fil: Raviolo, Mónica Ana. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina
Fil: Solana, M. E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Novoa, M. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Gualdesi, María Soledad. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina
Fil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Briñon. M. C.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina
description Chagas disease is caused by Trypanosoma cruzi (T. cruzi) leading to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available using drugs such as benznidazole and nifurtimox. Here, C6-alkyl(2aec) and N1-acyl (3aec) derivatives of Allopurinol (Allop, compound with activity against T. cruzi) were synthesized in good yields and their structures were unambiguously characterized. Only 2a, 2b and 3c showed inhibitory activity against the proliferative stages of the parasite when tested at 1 mg mL1 with the 3c derivative exhibiting an IC50 value similar to that of Allop and not being toxic for mammalian cells. Relevant pharmaceutical physicochemical properties (pKa, stability, solubility, lipophilicity) were also determined as well by using Lipinski?s rule, polar surface area and molecular rigidity. Taken together, the results demonstrated that the studied derivatives had optimal properties for bioavailability and oral absorption. For the stability studies, Micellar Liquid Chromatography was used as the analytical method which was fully validated according to the FDA guidelines and shown to be a suitable, sensitive and simple method for routine analysis of these Allop derivatives.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
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/11336/8511
Raviolo, Mónica Ana; Solana, M. E.; Novoa, M. M.; Gualdesi, María Soledad; Alba Soto, Catalina Dirney; et al.; Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi; Elsevier Masson; European Journal Of Medical Chemistry; 69; 8-2013; 455-464
0223-5234
url http://hdl.handle.net/11336/8511
identifier_str_mv Raviolo, Mónica Ana; Solana, M. E.; Novoa, M. M.; Gualdesi, María Soledad; Alba Soto, Catalina Dirney; et al.; Synthesis, physicochemical properties of allopurinol derivatives and their biological activity against Trypanosoma cruzi; Elsevier Masson; European Journal Of Medical Chemistry; 69; 8-2013; 455-464
0223-5234
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523413005631
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2013.08.045
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier Masson
publisher.none.fl_str_mv Elsevier Masson
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 13.001348

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