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dc.contributor.authorSt?pnicki, P.*
dc.contributor.authorWronikowska-Denysiuk, O.*
dc.contributor.authorZi?ba, A.*
dc.contributor.authorTargowska-Duda, K.M.*
dc.contributor.authorBartyzel, A.*
dc.contributor.authorWróbel, M.Z.*
dc.contributor.authorWróbel, T.M.*
dc.contributor.authorSza?aj, K.*
dc.contributor.authorChodkowski, A.*
dc.contributor.authorMirecka, K.*
dc.contributor.authorBudzy?ska, B.*
dc.contributor.authorFornal, E.*
dc.contributor.authorTur?o, J.*
dc.contributor.authorCastro Pérez, María de los Ángeles*
dc.contributor.authorKaczor, A.A.*
dc.date.accessioned2025-09-12T11:46:41Z
dc.date.available2025-09-12T11:46:41Z
dc.date.issued2023
dc.identifier.citationSt?pnicki P, Wronikowska-Denysiuk O, Zi?ba A, Targowska-Duda KM, Bartyzel A, Wróbel MZ, et al. Novel multi-target ligands of dopamine and serotonin receptors for the treatment of schizophrenia based on indazole and piperazine scaffolds-synthesis, biological activity, and structural evaluation. Journal of enzyme inhibition and medicinal chemistry. 2023;38(1):2209828.
dc.identifier.issn1475-6374
dc.identifier.otherhttps://portalcientifico.sergas.gal//documentos/6473478fc0b3b1384998a58f
dc.identifier.urihttp://hdl.handle.net/20.500.11940/21792
dc.description.abstractSchizophrenia is a chronic mental disorder that is not satisfactorily treated with available antipsychotics. The presented study focuses on the search for new antipsychotics by optimising the compound D2AAK3, a multi-target ligand of G-protein-coupled receptors (GPCRs), in particular D2, 5-HT1A, and 5-HT2A receptors. Such receptor profile may be beneficial for the treatment of schizophrenia. Compounds 1-16 were designed, synthesised, and subjected to further evaluation. Their affinities for the above-mentioned receptors were assessed in radioligand binding assays and efficacy towards them in functional assays. Compounds 1 and 10, selected based on their receptor profile, were subjected to in vivo tests to evaluate their antipsychotic activity, and effect on memory and anxiety processes. Molecular modelling was performed to investigate the interactions of the studied compounds with D2, 5-HT1A, and 5-HT2A receptors on the molecular level. Finally, X-ray study was conducted for compound 1, which revealed its stable conformation in the solid state.
dc.description.sponsorshipThis work was supported by the National Science Centre (NCN, Poland) under the OPUS Grant 2017/27/B/NZ7/01767 and UMO-2021/43/B/NZ7/01732 (to A.A.K). Calculations were partially performed under a computational grant by Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), Warsaw, Poland, Grant Number G85-948 (to A.A.K.). Molecular modelling was performed under DS33 grant from Medical University of Lublin (to A.A.K). In vitro pharmacology assays were performed with support from the Spanish Ministry of Economy and Competitiveness (MINECO) (Grant Number PID2020-119754GB-I00 to M.C.). The study was also supported in part by an Internal PB Grant for PhD students (Medical University of Lublin, Poland) in terms of in~vivo studies, Grant Number PBsd21 (to P.S.). Preliminary synthesis was partially performed with support from the Medical University of Warsaw Student Mini-Grant Number FW26/NM1/16/16. M. C. acknowledges technical assistance from Borja Blanco Babarro, with financial support from European Union-NextGenerationEU (Programa Investigo 2022, XUNTA de Galicia).
dc.languageeng
dc.rightsAttribution 4.0 International (CC BY 4.0)*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshHumans *
dc.subject.meshSchizophrenia *
dc.subject.meshPiperazine *
dc.subject.meshDopamine *
dc.subject.meshLigands *
dc.subject.meshIndazoles *
dc.subject.meshSerotonin *
dc.subject.meshReceptors, Serotonin*
dc.subject.meshAntipsychotic Agents *
dc.subject.meshReceptor, Serotonin, 5-HT1A*
dc.titleNovel multi-target ligands of dopamine and serotonin receptors for the treatment of schizophrenia based on indazole and piperazine scaffolds-synthesis, biological activity, and structural evaluation
dc.typeArtigo
dc.authorsophosSt?pnicki, P.; Wronikowska-Denysiuk, O.; Zi?ba, A.; Targowska-Duda, K.M.; Bartyzel, A.; Wróbel, M.Z.; Wróbel, T.M.; Sza?aj, K.; Chodkowski, A.; Mirecka, K.; Budzy?ska, B.; Fornal, E.; Tur?o, J.; Castro, M.; Kaczor, A.A.
dc.identifier.doi10.1080/14756366.2023.2209828
dc.identifier.sophos6473478fc0b3b1384998a58f
dc.issue.number1
dc.journal.titleJournal of enzyme inhibition and medicinal chemistry*
dc.organizationInstituto de Investigación Sanitaria de Santiago de Compostela (IDIS)
dc.page.initial2209828
dc.relation.projectIDNational Science Centre (NCN, Poland) under the OPUS Grant [2017/27/B/NZ7/01767, UMO-2021/43/B/NZ7/01732]
dc.relation.projectIDInterdisciplinary Centre for Mathematical and Computational Modelling (ICM), Warsaw, Poland [G85-948, DS33]
dc.relation.projectIDMedical University of Lublin
dc.relation.projectIDSpanish Ministry of Economy and Competitiveness (MINECO) [PID2020-119754GB-I00, PBsd21]
dc.relation.projectIDMedical University of Warsaw Student Mini-Grant [FW26/NM1/16/16]
dc.relation.projectIDEuropean Union-NextGenerationEU
dc.relation.publisherversionhttps://doi.org/10.1080/14756366.2023.2209828
dc.rights.accessRightsopenAccess*
dc.subject.keywordIDIS
dc.typefidesArtículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis)
dc.typesophosArtículo Original
dc.volume.number38


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Attribution 4.0 International (CC BY 4.0)
Excepto si se señala otra cosa, la licencia del ítem se describe como Attribution 4.0 International (CC BY 4.0)