RT Journal Article
T1 Synthesis, Experimental and Computational Evaluation of SERAAK1 as a 5-HT2A Receptor Ligand
A1 Zięba, Agata
A1 Kędzierska, Ewa
A1 Jastrzębski, Michał K.
A1 Karcz, Tadeusz
A1 Olejarz-Maciej, Agnieszka
A1 Sumara, Agata
A1 Laitinen, Tuomo
A1 Wróbel, Tomasz M.
A1 Fornal, Emilia
A1 Castro Pérez, María de los Ángeles
A1 Kaczor, Agnieszka A.
K1 5-HT2A receptor
K1 ADMET
K1 Antidepressants
K1 Antipsychotics
K1 In vivo studies
K1 Molecular modeling
AB Many drug discovery efforts have identified potentially promising molecules; however, a common limitation of these reports is the lack of further experimental confirmation of pharmacokinetic properties and behavioral effects of discovered compounds. In this study, we aim to address this limitation. Therefore, we build on our previous virtual screening campaign by synthesizing, analyzing in silico, and evaluating experimentally the SERAAK1 compound, which was initially identified as a ligand for 5-HT1A, 5-HT2A, and D2 receptors. Through these investigations, we discovered that SERAAK1 binds to the orthosteric pocket of the 5-HT2A receptor in a similar mechanism to that known for marketed antipsychotic medications. Molecular dynamics simulations revealed that the SERAAK1 compound remains stable in the orthosteric binding pocket of the 5-HT2A receptor. The determination of the ADMET parameters indicated the directions for further optimization of the compounds. In vivo studies demonstrated the anxiolytic and antidepressant properties of the SERAAK1 compound.
PB MPDI
SN 1420-3049
YR 2025
FD 2025-05-14
LK https://hdl.handle.net/10347/41629
UL https://hdl.handle.net/10347/41629
LA eng
NO Zięba, A.; Kędzierska, E.; Jastrzębski, M.K.; Karcz, T.; Olejarz-Maciej, A.; Sumara, A.; Laitinen, T.; Wróbel, T.M.; Fornal, E.; Castro, M.; et al. Synthesis, Experimental and Computational Evaluation of SERAAK1 as a 5-HT2A Receptor Ligand. Molecules 2025, 30, 2165. https://doi.org/10.3390/ molecules30102165
NO The study was supported by a statutory funds grant from the Medical University of Lublin, Poland, to A.A.K. (grant number DS33), and an internal PB grant for Young Researchers to A.Z. (grant number PBsd22). We would like to thank the Biocenter Finland/DDCB for financial support and the CSC-IT Center for Science Ltd. (Finland) for the allocation of computational resources (T.L.).
DS Minerva
RD 28 abr 2026