Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays

Autores
Clemente, Camila Mara; Onnainty, Renée; Usseglio, Nadina Aimé; Granero, Gladys Ester; Ravetti, Soledad
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters.
Fil: Clemente, Camila Mara. Universidad Nacional de Villa María. Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Usseglio, Nadina Aimé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Ravetti, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; Argentina
Materia
PREFORMULATION
ANTIPARASITIC
PERMEABILITY
MENTHOL
PRODRUGS
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:11336/222424
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability AssaysClemente, Camila MaraOnnainty, RenéeUsseglio, Nadina AiméGranero, Gladys EsterRavetti, SoledadPREFORMULATIONANTIPARASITICPERMEABILITYMENTHOLPRODRUGShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters.Fil: Clemente, Camila Mara. Universidad Nacional de Villa María. Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Usseglio, Nadina Aimé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Ravetti, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; ArgentinaMDPI2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222424Clemente, Camila Mara; Onnainty, Renée; Usseglio, Nadina Aimé; Granero, Gladys Ester; Ravetti, Soledad; Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays; MDPI; Drugs and Drug Candidates; 2; 3; 9-2023; 770-7802813-2998CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2813-2998/2/3/38info:eu-repo/semantics/altIdentifier/doi/10.3390/ddc2030038info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:41Zoai:ri.conicet.gov.ar:11336/222424instacron: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:34982025-09-29 10:42:41.712CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
title Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
spellingShingle Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
Clemente, Camila Mara
PREFORMULATION
ANTIPARASITIC
PERMEABILITY
MENTHOL
PRODRUGS
title_short Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
title_full Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
title_fullStr Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
title_full_unstemmed Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
title_sort Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
dc.creator.none.fl_str_mv Clemente, Camila Mara
Onnainty, Renée
Usseglio, Nadina Aimé
Granero, Gladys Ester
Ravetti, Soledad
author Clemente, Camila Mara
author_facet Clemente, Camila Mara
Onnainty, Renée
Usseglio, Nadina Aimé
Granero, Gladys Ester
Ravetti, Soledad
author_role author
author2 Onnainty, Renée
Usseglio, Nadina Aimé
Granero, Gladys Ester
Ravetti, Soledad
author2_role author
author
author
author
dc.subject.none.fl_str_mv PREFORMULATION
ANTIPARASITIC
PERMEABILITY
MENTHOL
PRODRUGS
topic PREFORMULATION
ANTIPARASITIC
PERMEABILITY
MENTHOL
PRODRUGS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters.
Fil: Clemente, Camila Mara. Universidad Nacional de Villa María. Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Usseglio, Nadina Aimé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Ravetti, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; Argentina
description Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters.
publishDate 2023
dc.date.none.fl_str_mv 2023-09
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/11336/222424
Clemente, Camila Mara; Onnainty, Renée; Usseglio, Nadina Aimé; Granero, Gladys Ester; Ravetti, Soledad; Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays; MDPI; Drugs and Drug Candidates; 2; 3; 9-2023; 770-780
2813-2998
CONICET Digital
CONICET
url http://hdl.handle.net/11336/222424
identifier_str_mv Clemente, Camila Mara; Onnainty, Renée; Usseglio, Nadina Aimé; Granero, Gladys Ester; Ravetti, Soledad; Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays; MDPI; Drugs and Drug Candidates; 2; 3; 9-2023; 770-780
2813-2998
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.mdpi.com/2813-2998/2/3/38
info:eu-repo/semantics/altIdentifier/doi/10.3390/ddc2030038
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
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 13.070432

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