RT Journal Article
T1 Multitarget Derivatives of D2AAK1 as Potential Antipsychotics: The Effect of Substitution in the Indole Moiety
A1 Kondej, Magda
A1 Wróbel, Tomasz M.
A1 Targowska-Duda, Katarzyna M.
A1 Martínez Rodríguez, Antón Leandro
A1 Koszła, Oliwia
A1 Stępnicki, Piotr
A1 Zięba, Agata
A1 Paz, Alba
A1 Wronikowska-Denysiuk, Olga
A1 Loza García, María Isabel
A1 Castro Pérez, María de los Ángeles
A1 Kaczor, Agnieszka A.
K1 Antipsychotics
K1 Behavioral studies
K1 G protein-coupled receptors
K1 Multitarget drugs
K1 Schizophrenia
AB Schizophrenia is a complex disease which is best treated with multitarget drugs, such as atypical antipsychotics. Previously, using structure-based virtual screening, we found a virtual hit, D2AAK1, with nanomolar affinity for dopamine and serotonin receptors important in schizophrenia pharmacotherapy. As a part of an optimization campaign of D2AAK1, we obtained 17 derivatives that also display a multitarget profile. Selected compounds were tested against off-targets in schizophrenia, i. e., histamine H1 receptor and muscarinic M1 receptor, and these did not display considerable affinity for these receptors. The two most promising compounds were subjected to behavioral studies. These compounds decreased amphetamine-induced hyperactivity in mice which indicates their antipsychotic potential. The compounds did not interfere with the memory consolidation in mice, as determined in the passive avoidance test. The favorable pharmacological profile of these compounds was rationalized using molecular modeling.
PB John Wiley and Sons Ltd
SN 1860-7179
YR 2022
FD 2022-06-17
LK https://hdl.handle.net/10347/39461
UL https://hdl.handle.net/10347/39461
LA eng
NO Kondej, M., Wróbel, T. M., Targowska-Duda, K. M., Leandro Martínez, A., Koszła, O., Stępnicki, P., Zięba, A., Paz, A., Wronikowska-Denysiuk, O., Loza, M. I., Castro, M., & Kaczor, A. A. (2022). Multitarget Derivatives of D2AAK1 as Potential Antipsychotics: The Effect of Substitution in the Indole Moiety. ChemMedChem, 17(15), e202200238.
DS Minerva
RD 29 abr 2026