Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin
ABSTRACT: Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determi...
- Autores:
-
Pereañez Jiménez, Jaime Andrés
Preciado Rojo, Lina María
Rey Suárez, Paola
Núñez Rangel, Vitelbina
Comer, Jeffrey
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2018
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/20585
- Acceso en línea:
- http://hdl.handle.net/10495/20585
- Palabra clave:
- Flavonoides
Flavonoids
Venenos de Serpiente
Snake Venoms
Simulación de Dinámica Molecular
Molecular Dynamics Simulation
Inhibidores de la Metaloproteinasa de la Matriz
Matrix Metalloproteinase Inhibitors
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by/2.5/co/
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UDEA2 |
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Repositorio UdeA |
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|
dc.title.spa.fl_str_mv |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
title |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
spellingShingle |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin Flavonoides Flavonoids Venenos de Serpiente Snake Venoms Simulación de Dinámica Molecular Molecular Dynamics Simulation Inhibidores de la Metaloproteinasa de la Matriz Matrix Metalloproteinase Inhibitors |
title_short |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
title_full |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
title_fullStr |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
title_full_unstemmed |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
title_sort |
Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin |
dc.creator.fl_str_mv |
Pereañez Jiménez, Jaime Andrés Preciado Rojo, Lina María Rey Suárez, Paola Núñez Rangel, Vitelbina Comer, Jeffrey |
dc.contributor.author.none.fl_str_mv |
Pereañez Jiménez, Jaime Andrés Preciado Rojo, Lina María Rey Suárez, Paola Núñez Rangel, Vitelbina Comer, Jeffrey |
dc.subject.decs.none.fl_str_mv |
Flavonoides Flavonoids Venenos de Serpiente Snake Venoms Simulación de Dinámica Molecular Molecular Dynamics Simulation Inhibidores de la Metaloproteinasa de la Matriz Matrix Metalloproteinase Inhibitors |
topic |
Flavonoides Flavonoids Venenos de Serpiente Snake Venoms Simulación de Dinámica Molecular Molecular Dynamics Simulation Inhibidores de la Metaloproteinasa de la Matriz Matrix Metalloproteinase Inhibitors |
description |
ABSTRACT: Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determine the inhibitory ability of ten flavonoids on the in-vitro proteolytic activity of Bothrops atrox venom and on the hemorrhagic, edema-forming and myonecrotic activities of Batx-I, the most abundant metalloproteinase isolated from this venom. Myricetin was the most active compound, exhibiting an IC50 value of 150 µM and 1021 µM for the inhibition of proteolytic and hemorrhagic activity, respectively. Independent injection experiments, with a concentration of 1600 µM of myricetin administered locally, immediately after toxin injection, demonstrated a reduction of 28 ± 6% in the hemorrhagic lesion. Additionally, myricetin at concentrations 800, 1200 and 1600 µM promoted a reduction in plasma creatine kinase activity induced by Batx-I of 21 ± 2%, 60 ± 5% and 63 ± 2%, respectively. Molecular dynamics simulations coupled with the adaptive biasing method suggest that myricetin can bind to the metalloproteinase active site via formation of hydrogen bonds between the hydroxyl groups 3’, 4’ and 5’ of the benzyl moiety and amino acid Glu143 of the metalloproteinase. The hydroxyl substitution pattern of myricetin appears to be essential for its inhibitory activity. Based on this evidence, myricetin constitutes a candidate for the development of inhibitors to reduce local tissue damage in snakebite envenomation. |
publishDate |
2018 |
dc.date.issued.none.fl_str_mv |
2018 |
dc.date.accessioned.none.fl_str_mv |
2021-07-02T13:12:39Z |
dc.date.available.none.fl_str_mv |
2021-07-02T13:12:39Z |
dc.type.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.hasversion.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
dc.type.local.spa.fl_str_mv |
Artículo de investigación |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
dc.identifier.citation.spa.fl_str_mv |
Preciado, L., Comer, J., Núñez, V., Rey-Súarez, P., & Pereañez, J. (2018). Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin. Molecules, 23(10), 2662. MDPI AG. Retrieved from http://dx.doi.org/10.3390/molecules23102662 |
dc.identifier.issn.none.fl_str_mv |
1420-3049 |
dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10495/20585 |
dc.identifier.doi.none.fl_str_mv |
10.3390/molecules23102662 |
identifier_str_mv |
Preciado, L., Comer, J., Núñez, V., Rey-Súarez, P., & Pereañez, J. (2018). Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin. Molecules, 23(10), 2662. MDPI AG. Retrieved from http://dx.doi.org/10.3390/molecules23102662 1420-3049 10.3390/molecules23102662 |
url |
http://hdl.handle.net/10495/20585 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Molecules |
dc.rights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by/2.5/co/ |
dc.rights.accessrights.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.creativecommons.spa.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by/2.5/co/ http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
dc.format.extent.spa.fl_str_mv |
15 |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
MDPI |
dc.publisher.group.spa.fl_str_mv |
Toxinología Alternativas Terapéuticas y Alimentarias |
dc.publisher.place.spa.fl_str_mv |
Basilea, Suiza |
institution |
Universidad de Antioquia |
bitstream.url.fl_str_mv |
http://bibliotecadigital.udea.edu.co/bitstream/10495/20585/1/Perea%c3%b1ezJaime_2018_SnakeVenomMetalloproteinase.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/20585/2/license_rdf http://bibliotecadigital.udea.edu.co/bitstream/10495/20585/3/license.txt |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad de Antioquia |
repository.mail.fl_str_mv |
andres.perez@udea.edu.co |
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1812173106786074624 |
spelling |
Pereañez Jiménez, Jaime AndrésPreciado Rojo, Lina MaríaRey Suárez, PaolaNúñez Rangel, VitelbinaComer, Jeffrey2021-07-02T13:12:39Z2021-07-02T13:12:39Z2018Preciado, L., Comer, J., Núñez, V., Rey-Súarez, P., & Pereañez, J. (2018). Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin. Molecules, 23(10), 2662. MDPI AG. Retrieved from http://dx.doi.org/10.3390/molecules231026621420-3049http://hdl.handle.net/10495/2058510.3390/molecules23102662ABSTRACT: Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determine the inhibitory ability of ten flavonoids on the in-vitro proteolytic activity of Bothrops atrox venom and on the hemorrhagic, edema-forming and myonecrotic activities of Batx-I, the most abundant metalloproteinase isolated from this venom. Myricetin was the most active compound, exhibiting an IC50 value of 150 µM and 1021 µM for the inhibition of proteolytic and hemorrhagic activity, respectively. Independent injection experiments, with a concentration of 1600 µM of myricetin administered locally, immediately after toxin injection, demonstrated a reduction of 28 ± 6% in the hemorrhagic lesion. Additionally, myricetin at concentrations 800, 1200 and 1600 µM promoted a reduction in plasma creatine kinase activity induced by Batx-I of 21 ± 2%, 60 ± 5% and 63 ± 2%, respectively. Molecular dynamics simulations coupled with the adaptive biasing method suggest that myricetin can bind to the metalloproteinase active site via formation of hydrogen bonds between the hydroxyl groups 3’, 4’ and 5’ of the benzyl moiety and amino acid Glu143 of the metalloproteinase. The hydroxyl substitution pattern of myricetin appears to be essential for its inhibitory activity. Based on this evidence, myricetin constitutes a candidate for the development of inhibitors to reduce local tissue damage in snakebite envenomation.COL001447615application/pdfengMDPIToxinología Alternativas Terapéuticas y AlimentariasBasilea, Suizainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by/4.0/Inhibition of a Snake Venom Metalloproteinase by the Flavonoid MyricetinFlavonoidesFlavonoidsVenenos de SerpienteSnake VenomsSimulación de Dinámica MolecularMolecular Dynamics SimulationInhibidores de la Metaloproteinasa de la MatrizMatrix Metalloproteinase InhibitorsMoleculesMolecules1152310ORIGINALPereañezJaime_2018_SnakeVenomMetalloproteinase.pdfPereañezJaime_2018_SnakeVenomMetalloproteinase.pdfArtículo de investigaciónapplication/pdf837907http://bibliotecadigital.udea.edu.co/bitstream/10495/20585/1/Perea%c3%b1ezJaime_2018_SnakeVenomMetalloproteinase.pdf68aad2c0684b93f0cf71235f82bdc68cMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927http://bibliotecadigital.udea.edu.co/bitstream/10495/20585/2/license_rdf1646d1f6b96dbbbc38035efc9239ac9cMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/20585/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5310495/20585oai:bibliotecadigital.udea.edu.co:10495/205852021-07-02 08:19:17.973Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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 |