RT Journal Article
T1 N-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1Hbenzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic
A1 Kaczor, Agnieszka A.
A1 Targowska-Duda, Katarzyna M.
A1 García Silva, Andrea
A1 Kondej, Magda
A1 Biała, Grażyna
A1 Castro Pérez, María de los Ángeles
K1 Antipsychotics
K1 Behavioral Studies
K1 Drug Design
K1 In Vitro Studies
K1 Molecular Modeling
K1 Schizophrenia
AB N-(2-hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol -1-yl)propyl]piperidine-4-carboxamide (D2AAK4) is a multitarget ligand of aminergic G protein-coupled receptors (GPCRs) identified in structure-based virtual screening. Here we present detailed in vitro, in silico and in vivo investigations of this virtual hit. D2AAK4 has an atypical antipsychotic profile and low affinity to off-targets. It interacts with aminergic GPCRs, forming an electrostatic interaction between its protonatable nitrogen atom and the conserved Asp 3.32 of the receptors. At the dose of 100 mg/kg D2AAK4 decreases amphetamine-induced hyperactivity predictive of antipsychotic activity, improves memory consolidation in passive avoidance test and has anxiogenic properties in elevated plus maze test (EPM). Further optimization of the virtual hit D2AAK4 will be aimed to balance its multitarget profile and to obtain analogs with anxiolytic activity.
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/21687
UL http://hdl.handle.net/10347/21687
LA eng
NO Kaczor, A., Targowska-Duda, K., Silva, A., Kondej, M., Biała, G., & Castro, M. (2020). N-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H- benzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic. Biomolecules, 10(2), 349. https://doi.org/10.3390/biom10020349
NO The research was performed under OPUS grant from National Science Center (NCN, Poland), grant number 2017/27/B/NZ7/01767 (to A.A.K). Calculations were partially performed under a computational grant by Interdisciplinary Center for Mathematical and Computational Modeling (ICM), Warsaw, Poland, grant number G30-18 (to A.A.K.), under resources and licenses from CSC, Finland (to A.A.K). In vitro pharmacology assays were performed with support from the Spanish Ministry of Economy and Competitiveness (MINECO) (grant number SAF2014-57138-C2-1-R to M.C.). A.G.S. acknowledges funding from XUNTA de Galicia (Spain)
DS Minerva
RD 24 abr 2026