Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design

Autores
Goyzueta-Mamani, Luis Daniel; Barazorda-Ccahuana, Haruna Luz; Candia-Puma, Mayron Antonio; Galdino, Alexsandro Sobreira; Machado-de-Avila, Ricardo Andrez; Giunchetti, Rodolfo Cordeiro; Medina-Franco, José L.; Florin-Christensen, Mónica; Ferraz Coelho, Eduardo Antonio; Chavez Fumagalli, Miguel Angel
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite’s N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite’s changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.
Instituto de Patobiología
Fil: Goyzueta-Mamani, Luis Daniel. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fil: Barazorda-Ccahuana, Haruna Luz. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fil: Candia-Puma, Mayron Antonio. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fil: Candia-Puma, Mayron Antonio. Universidad Católica de Santa María. Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas; Perú
Fil: Galdino, Alexsandro Sobreira. Universidade Federal São João Del-Rei. Laboratório de Biotecnologia de Microrganismos; Brasil
Fil: Machado-de-Avila, Ricardo Andrez. Universidade do Extremo Sul Catarinense. Programa de Pós-Graduação em Ciências da Saúde; Brasil
Fil: Giunchetti, Rodolfo Cordeiro. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Biologia das Interações Celulares; Brasil
Fil: Giunchetti, Rodolfo Cordeiro. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT); Brasil
Fil: Medina-Franco, José L. Universidad Nacional Autónoma de México. School of Chemistry. Department of Pharmacy. DIFACQUIM Research Group; México
Fil: Florin-Christensen, Mónica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Florin-Christensen, Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferraz Coelho, Eduardo Antonio. Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical; Brasil
Fil: Ferraz Coelho, Eduardo Antonio. Universidade Federal de Minas Gerais. Colégio Técnico da Universidade Federal de Minas Gerais (COLTEC). Departamento de Patologia Clínica; Brasil
Fil: Chavez Fumagalli, Miguel Angel. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fuente
Frontiers in Pharmacology 15 : 1403203 (May 2024)
Materia
Leishmaniosis
Oligosaccharides
Glucosidases
Computer Software
Leishmania infantum
Oligosacáridos
Glucosidasa
Programas de Ordenador
Natural Products
Productos Naturales
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/20289
Acceder
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spelling Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug designGoyzueta-Mamani, Luis DanielBarazorda-Ccahuana, Haruna LuzCandia-Puma, Mayron AntonioGaldino, Alexsandro SobreiraMachado-de-Avila, Ricardo AndrezGiunchetti, Rodolfo CordeiroMedina-Franco, José L.Florin-Christensen, MónicaFerraz Coelho, Eduardo AntonioChavez Fumagalli, Miguel AngelLeishmaniosisOligosaccharidesGlucosidasesComputer SoftwareLeishmania infantumOligosacáridosGlucosidasaProgramas de OrdenadorNatural ProductsProductos NaturalesVisceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite’s N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite’s changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.Instituto de PatobiologíaFil: Goyzueta-Mamani, Luis Daniel. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; PerúFil: Barazorda-Ccahuana, Haruna Luz. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; PerúFil: Candia-Puma, Mayron Antonio. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; PerúFil: Candia-Puma, Mayron Antonio. Universidad Católica de Santa María. Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas; PerúFil: Galdino, Alexsandro Sobreira. Universidade Federal São João Del-Rei. Laboratório de Biotecnologia de Microrganismos; BrasilFil: Machado-de-Avila, Ricardo Andrez. Universidade do Extremo Sul Catarinense. Programa de Pós-Graduação em Ciências da Saúde; BrasilFil: Giunchetti, Rodolfo Cordeiro. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Biologia das Interações Celulares; BrasilFil: Giunchetti, Rodolfo Cordeiro. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT); BrasilFil: Medina-Franco, José L. Universidad Nacional Autónoma de México. School of Chemistry. Department of Pharmacy. DIFACQUIM Research Group; MéxicoFil: Florin-Christensen, Mónica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Florin-Christensen, Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferraz Coelho, Eduardo Antonio. Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical; BrasilFil: Ferraz Coelho, Eduardo Antonio. Universidade Federal de Minas Gerais. Colégio Técnico da Universidade Federal de Minas Gerais (COLTEC). Departamento de Patologia Clínica; BrasilFil: Chavez Fumagalli, Miguel Angel. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; PerúFrontiers Media2024-11-15T10:01:23Z2024-11-15T10:01:23Z2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/20289https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1403203/full1663-9812https://doi.org/10.3389/fphar.2024.1403203Frontiers in Pharmacology 15 : 1403203 (May 2024)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-06-11T09:53:58Zoai:localhost:20.500.12123/20289instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-06-11 09:53:59.059INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
title Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
spellingShingle Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
Goyzueta-Mamani, Luis Daniel
Leishmaniosis
Oligosaccharides
Glucosidases
Computer Software
Leishmania infantum
Oligosacáridos
Glucosidasa
Programas de Ordenador
Natural Products
Productos Naturales
title_short Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
title_full Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
title_fullStr Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
title_full_unstemmed Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
title_sort Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
dc.creator.none.fl_str_mv Goyzueta-Mamani, Luis Daniel
Barazorda-Ccahuana, Haruna Luz
Candia-Puma, Mayron Antonio
Galdino, Alexsandro Sobreira
Machado-de-Avila, Ricardo Andrez
Giunchetti, Rodolfo Cordeiro
Medina-Franco, José L.
Florin-Christensen, Mónica
Ferraz Coelho, Eduardo Antonio
Chavez Fumagalli, Miguel Angel
author Goyzueta-Mamani, Luis Daniel
author_facet Goyzueta-Mamani, Luis Daniel
Barazorda-Ccahuana, Haruna Luz
Candia-Puma, Mayron Antonio
Galdino, Alexsandro Sobreira
Machado-de-Avila, Ricardo Andrez
Giunchetti, Rodolfo Cordeiro
Medina-Franco, José L.
Florin-Christensen, Mónica
Ferraz Coelho, Eduardo Antonio
Chavez Fumagalli, Miguel Angel
author_role author
author2 Barazorda-Ccahuana, Haruna Luz
Candia-Puma, Mayron Antonio
Galdino, Alexsandro Sobreira
Machado-de-Avila, Ricardo Andrez
Giunchetti, Rodolfo Cordeiro
Medina-Franco, José L.
Florin-Christensen, Mónica
Ferraz Coelho, Eduardo Antonio
Chavez Fumagalli, Miguel Angel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leishmaniosis
Oligosaccharides
Glucosidases
Computer Software
Leishmania infantum
Oligosacáridos
Glucosidasa
Programas de Ordenador
Natural Products
Productos Naturales
topic Leishmaniosis
Oligosaccharides
Glucosidases
Computer Software
Leishmania infantum
Oligosacáridos
Glucosidasa
Programas de Ordenador
Natural Products
Productos Naturales
dc.description.none.fl_txt_mv Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite’s N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite’s changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.
Instituto de Patobiología
Fil: Goyzueta-Mamani, Luis Daniel. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fil: Barazorda-Ccahuana, Haruna Luz. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fil: Candia-Puma, Mayron Antonio. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
Fil: Candia-Puma, Mayron Antonio. Universidad Católica de Santa María. Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas; Perú
Fil: Galdino, Alexsandro Sobreira. Universidade Federal São João Del-Rei. Laboratório de Biotecnologia de Microrganismos; Brasil
Fil: Machado-de-Avila, Ricardo Andrez. Universidade do Extremo Sul Catarinense. Programa de Pós-Graduação em Ciências da Saúde; Brasil
Fil: Giunchetti, Rodolfo Cordeiro. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Biologia das Interações Celulares; Brasil
Fil: Giunchetti, Rodolfo Cordeiro. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT); Brasil
Fil: Medina-Franco, José L. Universidad Nacional Autónoma de México. School of Chemistry. Department of Pharmacy. DIFACQUIM Research Group; México
Fil: Florin-Christensen, Mónica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Florin-Christensen, Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferraz Coelho, Eduardo Antonio. Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical; Brasil
Fil: Ferraz Coelho, Eduardo Antonio. Universidade Federal de Minas Gerais. Colégio Técnico da Universidade Federal de Minas Gerais (COLTEC). Departamento de Patologia Clínica; Brasil
Fil: Chavez Fumagalli, Miguel Angel. Universidad Católica de Santa María. Vicerrectorado de Investigación. Computational Biology and Chemistry Research Group; Perú
description Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite’s N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite’s changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.
publishDate 2024
dc.date.none.fl_str_mv 2024-11-15T10:01:23Z
2024-11-15T10:01:23Z
2024-05
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/20.500.12123/20289
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1403203/full
1663-9812
https://doi.org/10.3389/fphar.2024.1403203
url http://hdl.handle.net/20.500.12123/20289
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1403203/full
https://doi.org/10.3389/fphar.2024.1403203
identifier_str_mv 1663-9812
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Pharmacology 15 : 1403203 (May 2024)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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