Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment

Autores
Gómez Chávez, José Leonardo; Conti, German Andrés; Miranda, Matias Orlando; Angelina, Emilio Luis; Peruchena, Nelida Maria
Año de publicación
2023
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Background: The chronic stage of Chagas disease is characterized by severe cardiomyopathy caused by infection with the parasite Trypanosoma cruzi. Through molecular dynamics simulations, compounds derived from Cymbopogon citratus have demonstrated promising potential as ligands for proteins involved in this stage of the disease, displaying favorable binding energies. These interactions between the ligand-protein complexes may explain the observed effects of relieving this pathology by reducing amastigote nets and inflammatory infiltrates in the cardiac tissue of mice.In this study, we analyzed the key interactions between compounds derived from Cymbopogon citratus and the most significant proteins associated with Chagas disease in mice.Results: Ptgs2, Hck, and Csf1r complexes have demonstrated excellent binding free energies (ΔGbind) compared to specific inhibitors targeting these proteins. An analysis based on Quantum Theory of Atoms in Molecules (QTAIM) revealed that, in the case of Ptgs2, it exhibits a high affinity for binding to molecules with both a polar and non-polar (unsaturated) moiety, such as certain terpenes. This is attributed to the characteristic triad in its active site, consisting of arginine, tyrosine, and aspartic acid, which can attract the polar part of ligands. Furthermore, due to the presence of numerous non-polar residues in the active site, a significant number of non-polar interactions are formed, stabilizing the interaction with the formed complexes.Similarly, Hck and Csf1r also show a strong tendency to bind to terpenes with structural unsaturations, leading to the formation of numerous non-polar interactions within the complexes. Although these non-polar interactions are weaker compared to polar interactions, they still contribute to stabilizing and forming a high affinity with these complexes.Conclusions: This study highlights the importance of interactions between compounds derived from Cymbopogon citratus and key proteins involved in Chagas disease in mice. Furthermore, the fact that multiple compounds bind to different target proteins suggests that the observed alleviation of symptoms in the chronic phase of Chagas disease may be due to a collective action of multiple molecules on different targets. These findings encourage further investigation of Cymbopogon citratus as a potential alternative for Chagas disease treatment.
Fil: Gómez Chávez, José Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Conti, German Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Miranda, Matias Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
XIII Argentine Congress of Bioinformatics and Computational Biology; XIII International Conference of the Iberoamerican Society of Bioinformatics; III Annual Meeting of the Ibero-American Artificial Intelligence Network for Big BioData
Rosario
Argentina
Asociación Argentina de Bioinformática y Biología Computacional
Materia
TRYPANOSOMA CRUZI
NETWORK PHARMACOLOGY
TERPENES
VIRTUAL SCREENING
QTAIM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/248031
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/248031
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network_name_str CONICET Digital (CONICET)
spelling Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease TreatmentGómez Chávez, José LeonardoConti, German AndrésMiranda, Matias OrlandoAngelina, Emilio LuisPeruchena, Nelida MariaTRYPANOSOMA CRUZINETWORK PHARMACOLOGYTERPENESVIRTUAL SCREENINGQTAIMhttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1Background: The chronic stage of Chagas disease is characterized by severe cardiomyopathy caused by infection with the parasite Trypanosoma cruzi. Through molecular dynamics simulations, compounds derived from Cymbopogon citratus have demonstrated promising potential as ligands for proteins involved in this stage of the disease, displaying favorable binding energies. These interactions between the ligand-protein complexes may explain the observed effects of relieving this pathology by reducing amastigote nets and inflammatory infiltrates in the cardiac tissue of mice.In this study, we analyzed the key interactions between compounds derived from Cymbopogon citratus and the most significant proteins associated with Chagas disease in mice.Results: Ptgs2, Hck, and Csf1r complexes have demonstrated excellent binding free energies (ΔGbind) compared to specific inhibitors targeting these proteins. An analysis based on Quantum Theory of Atoms in Molecules (QTAIM) revealed that, in the case of Ptgs2, it exhibits a high affinity for binding to molecules with both a polar and non-polar (unsaturated) moiety, such as certain terpenes. This is attributed to the characteristic triad in its active site, consisting of arginine, tyrosine, and aspartic acid, which can attract the polar part of ligands. Furthermore, due to the presence of numerous non-polar residues in the active site, a significant number of non-polar interactions are formed, stabilizing the interaction with the formed complexes.Similarly, Hck and Csf1r also show a strong tendency to bind to terpenes with structural unsaturations, leading to the formation of numerous non-polar interactions within the complexes. Although these non-polar interactions are weaker compared to polar interactions, they still contribute to stabilizing and forming a high affinity with these complexes.Conclusions: This study highlights the importance of interactions between compounds derived from Cymbopogon citratus and key proteins involved in Chagas disease in mice. Furthermore, the fact that multiple compounds bind to different target proteins suggests that the observed alleviation of symptoms in the chronic phase of Chagas disease may be due to a collective action of multiple molecules on different targets. These findings encourage further investigation of Cymbopogon citratus as a potential alternative for Chagas disease treatment.Fil: Gómez Chávez, José Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Conti, German Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Miranda, Matias Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaXIII Argentine Congress of Bioinformatics and Computational Biology; XIII International Conference of the Iberoamerican Society of Bioinformatics; III Annual Meeting of the Ibero-American Artificial Intelligence Network for Big BioDataRosarioArgentinaAsociación Argentina de Bioinformática y Biología ComputacionalAsociación Argentina de Bioinformática y Biología Computacional2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/248031Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment; XIII Argentine Congress of Bioinformatics and Computational Biology; XIII International Conference of the Iberoamerican Society of Bioinformatics; III Annual Meeting of the Ibero-American Artificial Intelligence Network for Big BioData; Rosario; Argentina; 2023; 65-65978-987-48989-7-5CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/http://2023.a2b2c.org.ar/BookOfAbstracts2023.pdfinfo:eu-repo/semantics/altIdentifier/url/http://2023.a2b2c.org.ar/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:44Zoai:ri.conicet.gov.ar:11336/248031instacron: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 09:57:44.881CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
title Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
spellingShingle Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
Gómez Chávez, José Leonardo
TRYPANOSOMA CRUZI
NETWORK PHARMACOLOGY
TERPENES
VIRTUAL SCREENING
QTAIM
title_short Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
title_full Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
title_fullStr Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
title_full_unstemmed Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
title_sort Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment
dc.creator.none.fl_str_mv Gómez Chávez, José Leonardo
Conti, German Andrés
Miranda, Matias Orlando
Angelina, Emilio Luis
Peruchena, Nelida Maria
author Gómez Chávez, José Leonardo
author_facet Gómez Chávez, José Leonardo
Conti, German Andrés
Miranda, Matias Orlando
Angelina, Emilio Luis
Peruchena, Nelida Maria
author_role author
author2 Conti, German Andrés
Miranda, Matias Orlando
Angelina, Emilio Luis
Peruchena, Nelida Maria
author2_role author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
NETWORK PHARMACOLOGY
TERPENES
VIRTUAL SCREENING
QTAIM
topic TRYPANOSOMA CRUZI
NETWORK PHARMACOLOGY
TERPENES
VIRTUAL SCREENING
QTAIM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: The chronic stage of Chagas disease is characterized by severe cardiomyopathy caused by infection with the parasite Trypanosoma cruzi. Through molecular dynamics simulations, compounds derived from Cymbopogon citratus have demonstrated promising potential as ligands for proteins involved in this stage of the disease, displaying favorable binding energies. These interactions between the ligand-protein complexes may explain the observed effects of relieving this pathology by reducing amastigote nets and inflammatory infiltrates in the cardiac tissue of mice.In this study, we analyzed the key interactions between compounds derived from Cymbopogon citratus and the most significant proteins associated with Chagas disease in mice.Results: Ptgs2, Hck, and Csf1r complexes have demonstrated excellent binding free energies (ΔGbind) compared to specific inhibitors targeting these proteins. An analysis based on Quantum Theory of Atoms in Molecules (QTAIM) revealed that, in the case of Ptgs2, it exhibits a high affinity for binding to molecules with both a polar and non-polar (unsaturated) moiety, such as certain terpenes. This is attributed to the characteristic triad in its active site, consisting of arginine, tyrosine, and aspartic acid, which can attract the polar part of ligands. Furthermore, due to the presence of numerous non-polar residues in the active site, a significant number of non-polar interactions are formed, stabilizing the interaction with the formed complexes.Similarly, Hck and Csf1r also show a strong tendency to bind to terpenes with structural unsaturations, leading to the formation of numerous non-polar interactions within the complexes. Although these non-polar interactions are weaker compared to polar interactions, they still contribute to stabilizing and forming a high affinity with these complexes.Conclusions: This study highlights the importance of interactions between compounds derived from Cymbopogon citratus and key proteins involved in Chagas disease in mice. Furthermore, the fact that multiple compounds bind to different target proteins suggests that the observed alleviation of symptoms in the chronic phase of Chagas disease may be due to a collective action of multiple molecules on different targets. These findings encourage further investigation of Cymbopogon citratus as a potential alternative for Chagas disease treatment.
Fil: Gómez Chávez, José Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Conti, German Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Miranda, Matias Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
XIII Argentine Congress of Bioinformatics and Computational Biology; XIII International Conference of the Iberoamerican Society of Bioinformatics; III Annual Meeting of the Ibero-American Artificial Intelligence Network for Big BioData
Rosario
Argentina
Asociación Argentina de Bioinformática y Biología Computacional
description Background: The chronic stage of Chagas disease is characterized by severe cardiomyopathy caused by infection with the parasite Trypanosoma cruzi. Through molecular dynamics simulations, compounds derived from Cymbopogon citratus have demonstrated promising potential as ligands for proteins involved in this stage of the disease, displaying favorable binding energies. These interactions between the ligand-protein complexes may explain the observed effects of relieving this pathology by reducing amastigote nets and inflammatory infiltrates in the cardiac tissue of mice.In this study, we analyzed the key interactions between compounds derived from Cymbopogon citratus and the most significant proteins associated with Chagas disease in mice.Results: Ptgs2, Hck, and Csf1r complexes have demonstrated excellent binding free energies (ΔGbind) compared to specific inhibitors targeting these proteins. An analysis based on Quantum Theory of Atoms in Molecules (QTAIM) revealed that, in the case of Ptgs2, it exhibits a high affinity for binding to molecules with both a polar and non-polar (unsaturated) moiety, such as certain terpenes. This is attributed to the characteristic triad in its active site, consisting of arginine, tyrosine, and aspartic acid, which can attract the polar part of ligands. Furthermore, due to the presence of numerous non-polar residues in the active site, a significant number of non-polar interactions are formed, stabilizing the interaction with the formed complexes.Similarly, Hck and Csf1r also show a strong tendency to bind to terpenes with structural unsaturations, leading to the formation of numerous non-polar interactions within the complexes. Although these non-polar interactions are weaker compared to polar interactions, they still contribute to stabilizing and forming a high affinity with these complexes.Conclusions: This study highlights the importance of interactions between compounds derived from Cymbopogon citratus and key proteins involved in Chagas disease in mice. Furthermore, the fact that multiple compounds bind to different target proteins suggests that the observed alleviation of symptoms in the chronic phase of Chagas disease may be due to a collective action of multiple molecules on different targets. These findings encourage further investigation of Cymbopogon citratus as a potential alternative for Chagas disease treatment.
publishDate 2023
dc.date.none.fl_str_mv 2023
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/248031
Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment; XIII Argentine Congress of Bioinformatics and Computational Biology; XIII International Conference of the Iberoamerican Society of Bioinformatics; III Annual Meeting of the Ibero-American Artificial Intelligence Network for Big BioData; Rosario; Argentina; 2023; 65-65
978-987-48989-7-5
CONICET Digital
CONICET
url http://hdl.handle.net/11336/248031
identifier_str_mv Ligand-Protein Interactions of Cymbopogon citratus Compounds and Their Implications for Chagas Disease Treatment; XIII Argentine Congress of Bioinformatics and Computational Biology; XIII International Conference of the Iberoamerican Society of Bioinformatics; III Annual Meeting of the Ibero-American Artificial Intelligence Network for Big BioData; Rosario; Argentina; 2023; 65-65
978-987-48989-7-5
CONICET Digital
CONICET
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dc.publisher.none.fl_str_mv Asociación Argentina de Bioinformática y Biología Computacional
publisher.none.fl_str_mv Asociación Argentina de Bioinformática y Biología Computacional
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