| Autor: |
Stępnicki P; Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland., Wronikowska-Denysiuk O; Independent Laboratory of Behavioral Studies, Chair of Biomedical Sciences, Faculty of Biomedicine, Medical University of Lublin, Lublin, Poland., Zięba A; Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland., Targowska-Duda KM; Department of Biopharmacy, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland., Bartyzel A; Department of General and Coordination Chemistry and Crystallography, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, Lublin, Poland., Wróbel MZ; Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland., Wróbel TM; Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland., Szałaj K; Department of Bioanalytics, Faculty of Biomedicine, Medical University of Lublin, Lublin, Poland., Chodkowski A; Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland., Mirecka K; Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland., Budzyńska B; Independent Laboratory of Behavioral Studies, Chair of Biomedical Sciences, Faculty of Biomedicine, Medical University of Lublin, Lublin, Poland., Fornal E; Department of Bioanalytics, Faculty of Biomedicine, Medical University of Lublin, Lublin, Poland., Turło J; Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland., Castro M; Department of Pharmacology, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Kaczor AA; Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland.; School of Pharmacy, University of Eastern Finland, Kuopio, Finland. |
| Abstrakt: |
Schizophrenia 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 D 2 , 5-HT 1A , and 5-HT 2A 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 D 2 , 5-HT 1A , and 5-HT 2A receptors on the molecular level. Finally, X-ray study was conducted for compound 1 , which revealed its stable conformation in the solid state. |
