A new antagonist of Caenorhabditis elegans glutamate-activated chloride channels with anthelmintic activity

dc.contributorDelfino, Jose Maria
dc.creatorTurani, Ornella
dc.creatorCastro, Maria Julia
dc.creatorFaraoni, María Belén
dc.creatorGerbino, Darío César
dc.creatorBouzat, Cecilia Beatriz
dc.date2020
dc.identifierhttp://hdl.handle.net/11336/161169
dc.identifierA new antagonist of Caenorhabditis elegans glutamate-activated chloride channels with anthelmintic activity; Primeras Jornadas Virtuales de la Sociedad Argentina de Biofísica; Argentina; 2020; 50-50
dc.identifier978-987-27591-8-6
dc.identifierCONICET Digital
dc.identifierCONICET
dc.descriptionNematode parasitosis causes mortality and morbidity in humans and losses in livestock and domestic animals. The acquisition of resistance to current anthelmintic drugs has prompted the search for new compounds for which the nematode Caenorhabditis elegans has emerged as a valuable platform. We have previously synthetized a library of compounds and determined that dibenzo[b,e]oxepin-11(6H)-one (doxepinone) reduces swimming rate, induces paralysis, and decreases the rate of pharyngeal pumping on C. elegans. To identify the drug targets, we performed a screening of strains carrying mutations in Cys-loop receptors involved in worm locomotion for determining resistance to doxepinone effects. A mutant strain that lacks subunit genes of the glutamate-gated chloride channels (GluCl), which are targets of the antiparasitic ivermectin, is resistant to doxepinone effects. To unravel the molecular mechanism, we measured whole-cell currents from GluClα1/β receptors expressed in mammalian cells. Glutamate elicits macroscopic currents whereas no responses are elicited by doxepinone, indicating that it is not an agonist of GluCls. Preincubation of the cell with doxepinone produces a significant decrease of the decay time constant and net charge of glutamate-elicited currents, indicating that it inhibits GluCls. Thus, we identify doxepinone as an attractive scaffold with promising anthelmintic activity and propose the inhibition of GluCls as a potential anthelmintic mechanism of action.
dc.descriptionFil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.descriptionFil: Castro, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.descriptionFil: Faraoni, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.descriptionFil: Gerbino, Darío César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.descriptionFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.descriptionPrimeras Jornadas Virtuales de la Sociedad Argentina de Biofísica
dc.descriptionArgentina
dc.descriptionSociedad Argentina de Biofísica
dc.formatapplication/pdf
dc.formatapplication/vnd.openxmlformats-officedocument.wordprocessingml.document
dc.formatapplication/pdf
dc.languageeng
dc.publisherSociedad Argentina de Biofísica
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subjectANTHELMINTIC ACTIVITY
dc.subjectCHLORIDE CHANNELS
dc.subjecthttps://purl.org/becyt/ford/1.6
dc.subjecthttps://purl.org/becyt/ford/1
dc.titleA new antagonist of Caenorhabditis elegans glutamate-activated chloride channels with anthelmintic activity
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typeinfo:eu-repo/semantics/conferenceObject
dc.typeinfo:ar-repo/semantics/documento de conferencia
dc.typeJornada
dc.typeBook
dc.coverageNacional


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