Evaluation of new antihypertensive drugs designed in silico using Thermolysin as a target

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datacite.alternateIdentifier.citationSaudi Pharmaceutical Journal, 28 (5), 592-582, 2020
datacite.alternateIdentifier.doi10.1016/j.jsps.2020.03.010
datacite.alternateIdentifier.issn1319-0164
datacite.creatorMacLeod-Carey, Desmond
datacite.creatorSolis-Céspedes, Eduardo
datacite.creatorLamazares, Emilio
datacite.creatorMena-Ulecia, Karel
datacite.date2020
datacite.rightsAcceso abierto
datacite.subjectAdme-tox
datacite.subjectAntihypertensive
datacite.subjectLigand Efficiency
datacite.subjectMm-gbsa
datacite.subjectMolecular Dynamics
datacite.subjectThermolysin
datacite.subjectLig 1022
datacite.subjectLig 1392
datacite.subjectLig 2177
datacite.subjectLig 3444
datacite.subjectLig 6199
datacite.subjectLig 783
datacite.subjectAntihypertensive Agent
datacite.subjectLig 1022
datacite.subjectLig 1392
datacite.subjectLig 2177
datacite.subjectLig 3444
datacite.subjectLig 6199
datacite.subjectLig 783
datacite.subjectThermolysin
datacite.subjectUnclassified Drug
datacite.subjectArticle
datacite.subjectComputer Model
datacite.subjectCrystal Structure
datacite.subjectDrug Targeting
datacite.subjectHuman
datacite.subjectMolecular Docking
datacite.subjectX Ray Crystallography
datacite.titleEvaluation of new antihypertensive drugs designed in silico using Thermolysin as a target
dc.contributor.authorMENA ULECIA, KAREL
dc.date.accessioned2025-10-06T14:22:08Z
dc.date.available2025-10-06T14:22:08Z
dc.description.abstractThe search for new therapies for the treatment of Arterial hypertension is a major concern in the scientific community. Here, we employ a computational biochemistry protocol to evaluate the performance of six compounds (Lig783, Lig1022, Lig1392, Lig2177, Lig3444 and Lig6199) to act as antihypertensive agents. This protocol consists of Docking experiments, efficiency calculations of ligands, molecular dynamics simulations, free energy, pharmacological and toxicological properties predictions (ADME-Tox) of the six ligands against Thermolysin. Our results show that the docked structures had an adequate orientation in the pocket of the Thermolysin enzymes, reproducing the X-ray crystal structure of Inhibitor-Thermolysin complexes in an acceptable way. The most promising candidates to act as antihypertensive agents among the series are Lig2177 and Lig3444. These compounds form the most stable ligand-Thermolysin complexes according to their binding free energy values obtained in the docking experiments as well as MM-GBSA decomposition analysis calculations. They present the lowest values of Ki, indicating that these ligands bind strongly to Thermolysin. Lig2177 was oriented in the pocket of Thermolysin in such a way that both OH of the dihydroxyl-amino groups to establish hydrogen bond interactions with Glu146 and Glu166. In the same way, Lig3444 interacts with Asp150, Glu143 and Tyr157. Additionally, Lig2177 and Lig3444 fulfill all the requirements established by Lipinski Veber and Pfizer 3/75 rules, indicating that these compounds could be safe compounds to be used as antihypertensive agents. We are confident that our computational biochemistry protocol can be used to evaluate and predict the behavior of a broad range of compounds designed in silicoagainst a protein target. © 2020 Elsevier B.V., All rights reserved.
dc.description.ia_keywordthermolysin, compounds, antihypertensive, protocol, agents, ligands, these
dc.formatPDF
dc.identifier.urihttps://repositoriodigital.uct.cl/handle/10925/6952
dc.language.isoen
dc.publisherElsevier BV
dc.relationinstname: ANID
dc.relationreponame: Repositorio Digital RI2.0
dc.rights.driverinfo:eu-repo/semantics/openAccess
dc.sourceSaudi Pharmaceutical Journal
dc.subject.ia_odsODS 7: Energía asequible y no contaminante
dc.subject.ia_oecd1nCiencias Naturales
dc.subject.ia_oecd2nCiencias Biológicas
dc.subject.ia_oecd3nBiología General
dc.type.driverinfo:eu-repo/semantics/article
dc.type.driverhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaireinfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
oaire.citationEdition2020
oaire.citationEndPage592
oaire.citationIssue5
oaire.citationStartPage582
oaire.citationTitleSaudi Pharmaceutical Journal
oaire.citationVolume28
oaire.fundingReferenceANID FONDECYT 11180650 (Iniciación)
oaire.licenseConditionObra bajo licencia Creative Commons Atribución-No Comercial-Sin Derivadas 4.0 Internacional
oaire.licenseCondition.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
oaire.resourceTypeArtículo
oaire.resourceType.enArticle
relation.isAuthorOfPublication7073b065-ad61-4799-9cbf-45500a019334
relation.isAuthorOfPublication.latestForDiscovery7073b065-ad61-4799-9cbf-45500a019334
uct.catalogadorjvu
uct.comunidadRecursos Naturalesen_US
uct.departamentoDepartamento de Ciencias Biológicas y Químicas
uct.facultadFacultad de Recursos Naturales
uct.indizacionScience Citation Index Expanded - SCIE
uct.indizacionScopus
uct.indizacionPubMed Central (PMC)
uct.indizacionEmbase
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