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dc.creatorMazzotta, Sarahes
dc.creatorCarullo, Gabrielees
dc.creatorSchiano Moriello, Anielloes
dc.creatorAmodeo, Pietroes
dc.creatorMarzo, Vincenzo Dies
dc.creatorVega Holm, Margaritaes
dc.creatorVitale, Rosa Mariaes
dc.creatorAiello, Francescaes
dc.creatorBrizzi, Antonellaes
dc.creatorPetrocellis, Luciano Dees
dc.date.accessioned2020-11-16T12:33:45Z
dc.date.available2020-11-16T12:33:45Z
dc.date.issued2020
dc.identifier.citationMazzotta, S., Carullo, ., Schiano Moriello, A., Amodeo, P., Marzo, V.D., Vega Holm, M.,...,Petrocellis, L.D. (2020). Design, Synthesis and In Vitro Experimental Validation of Novel TRPV4 Antagonists Inspired by Labdane Diterpenes. Mar Drugs, 18 (10), 1-18.
dc.identifier.issn1660-3397es
dc.identifier.urihttps://hdl.handle.net/11441/102629
dc.description.abstractLabdane diterpenes are widespread classes of natural compounds present in variety of marine and terrestrial organisms and plants. Many of them represents “natural libraries” of compounds with interesting biological activities due to differently functionalized drimane nucleus exploitable for potential pharmacological applications. The transient receptor potential channel subfamily V member 4 (TRPV4) channel has recently emerged as a pharmacological target for several respiratory diseases, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inspired by the labdane-like bicyclic core, a series of homodrimane-derived esters and amides was designed and synthesized by modifying the flexible tail in position 1 of (+)-sclareolide, an oxidized derivative of the bioactive labdane-type diterpene sclareol. The potency and selectivity towards rTRPV4 and hTRPV1 receptors were assessed by calcium influx cellular assays. Molecular determinants critical for eliciting TRPV4 antagonism were identified by structure-activity relationships. Among the selective TRPV4 antagonists identified, compound 6 was the most active with an IC50 of 5.3 μM. This study represents the first report of semisynthetic homodrimane TRPV4 antagonists, selective over TRPV1, and potentially useful as pharmacological tools for the development of novel TRPV4 channel modulators.es
dc.formatapplication/pdfes
dc.format.extent18 p.es
dc.language.isoenges
dc.publisherMDPIes
dc.relation.ispartofMar Drugs, 18 (10), 1-18.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectlabdane scaffoldes
dc.subjectbioactive diterpeneses
dc.subjectsclareolidees
dc.subjectstructure-activity relationshipses
dc.subjectTRPV4 channeles
dc.subjectamides/esterses
dc.subjectCOVID-19es
dc.subjectSARS-CoV-2es
dc.titleDesign, Synthesis and In Vitro Experimental Validation of Novel TRPV4 Antagonists Inspired by Labdane Diterpeneses
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Química Orgánica y Farmacéuticaes
dc.relation.publisherversionhttp://dx.doi.org/10.3390/md18100519es
dc.identifier.doi10.3390/md18100519es
dc.journaltitleMar Drugses
dc.publication.volumen18es
dc.publication.issue10es
dc.publication.initialPage1es
dc.publication.endPage18es

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