Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands
Аутори
Elek, MilicaĐoković, Nemanja
Frank, Annika
Oljačić, Slavica
Živković, Aleksandra
Nikolić, Katarina
Stark, Holger
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3R) receptor subtypes, which belong to the D2-like receptor family. The synthesis, in silico, and in vitro characterization of 10 dopamine receptor ligands were performed. Novel ligands were docked into the D2R and D3R crystal structures to examine the precise binding mode. A quantum mechanics/molecular mechanics study was performed to gain insights into the nature of the intermolecular interactions between the newly introduced pentafluorosulfanyl (SF5) moiety and D2R and D3R. A radioligand displacement assay determined that all of the ligands showed moderate-to-low nanomolar affinities at D2R and D3R, with a slight preference for D3R, which was confirmed in the in silico studies. N-{4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl}-4-(pentafluoro-λ6-sulfanyl)benzamide (7i) showed the... highest D3R affinity and selectivity (pKi values of 7.14 [D2R] and 8.42 [D3R]).
Кључне речи:
D2 receptor / D3 receptor / ligands / pentafluorosulfanyl / QM/MMИзвор:
Archiv der Pharmazie, 2021Издавач:
- Wiley-VCH Verlag
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1002/ardp.202000486
ISSN: 0365-6233
WoS: 000620193800001
Scopus: 2-s2.0-85101213290
Институција/група
PharmacyTY - JOUR AU - Elek, Milica AU - Đoković, Nemanja AU - Frank, Annika AU - Oljačić, Slavica AU - Živković, Aleksandra AU - Nikolić, Katarina AU - Stark, Holger PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3793 AB - Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3R) receptor subtypes, which belong to the D2-like receptor family. The synthesis, in silico, and in vitro characterization of 10 dopamine receptor ligands were performed. Novel ligands were docked into the D2R and D3R crystal structures to examine the precise binding mode. A quantum mechanics/molecular mechanics study was performed to gain insights into the nature of the intermolecular interactions between the newly introduced pentafluorosulfanyl (SF5) moiety and D2R and D3R. A radioligand displacement assay determined that all of the ligands showed moderate-to-low nanomolar affinities at D2R and D3R, with a slight preference for D3R, which was confirmed in the in silico studies. N-{4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl}-4-(pentafluoro-λ6-sulfanyl)benzamide (7i) showed the highest D3R affinity and selectivity (pKi values of 7.14 [D2R] and 8.42 [D3R]). PB - Wiley-VCH Verlag T2 - Archiv der Pharmazie T1 - Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands DO - 10.1002/ardp.202000486 ER -
@article{ author = "Elek, Milica and Đoković, Nemanja and Frank, Annika and Oljačić, Slavica and Živković, Aleksandra and Nikolić, Katarina and Stark, Holger", year = "2021", abstract = "Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3R) receptor subtypes, which belong to the D2-like receptor family. The synthesis, in silico, and in vitro characterization of 10 dopamine receptor ligands were performed. Novel ligands were docked into the D2R and D3R crystal structures to examine the precise binding mode. A quantum mechanics/molecular mechanics study was performed to gain insights into the nature of the intermolecular interactions between the newly introduced pentafluorosulfanyl (SF5) moiety and D2R and D3R. A radioligand displacement assay determined that all of the ligands showed moderate-to-low nanomolar affinities at D2R and D3R, with a slight preference for D3R, which was confirmed in the in silico studies. N-{4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl}-4-(pentafluoro-λ6-sulfanyl)benzamide (7i) showed the highest D3R affinity and selectivity (pKi values of 7.14 [D2R] and 8.42 [D3R]).", publisher = "Wiley-VCH Verlag", journal = "Archiv der Pharmazie", title = "Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands", doi = "10.1002/ardp.202000486" }
Elek, M., Đoković, N., Frank, A., Oljačić, S., Živković, A., Nikolić, K.,& Stark, H.. (2021). Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands. in Archiv der Pharmazie Wiley-VCH Verlag.. https://doi.org/10.1002/ardp.202000486
Elek M, Đoković N, Frank A, Oljačić S, Živković A, Nikolić K, Stark H. Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands. in Archiv der Pharmazie. 2021;. doi:10.1002/ardp.202000486 .
Elek, Milica, Đoković, Nemanja, Frank, Annika, Oljačić, Slavica, Živković, Aleksandra, Nikolić, Katarina, Stark, Holger, "Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands" in Archiv der Pharmazie (2021), https://doi.org/10.1002/ardp.202000486 . .