Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design
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 chall...
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| Format: | Artículo |
| Language: | Inglés |
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Frontiers Media
2024
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| Online Access: | 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 |
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| author | 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_browse | Barazorda-Ccahuana, Haruna Luz Candia-Puma, Mayron Antonio Chavez Fumagalli, Miguel Angel Ferraz Coelho, Eduardo Antonio Florin-Christensen, Mónica Galdino, Alexsandro Sobreira Giunchetti, Rodolfo Cordeiro Goyzueta-Mamani, Luis Daniel Machado-de-Avila, Ricardo Andrez Medina-Franco, José L. |
| 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_sort | Goyzueta-Mamani, Luis Daniel |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA20289 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| record_format | dspace |
| spelling | INTA202892024-11-15T10:05:54Z Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products : potential pH-dependent inhibition explored through computer-aided drug design 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 Leishmaniosis Oligosaccharides Glucosidases Computer Software Leishmania infantum Oligosacáridos Glucosidasa Programas de Ordenador Natural Products Productos Naturales 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 2024-11-15T10:01:23Z 2024-11-15T10:01:23Z 2024-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Frontiers Media Frontiers in Pharmacology 15 : 1403203 (May 2024) |
| spellingShingle | Leishmaniosis Oligosaccharides Glucosidases Computer Software Leishmania infantum Oligosacáridos Glucosidasa Programas de Ordenador Natural Products Productos Naturales 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 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 |
| 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_short | 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 |
| topic | Leishmaniosis Oligosaccharides Glucosidases Computer Software Leishmania infantum Oligosacáridos Glucosidasa Programas de Ordenador Natural Products Productos Naturales |
| 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 |
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