TY  - 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 . .

TY  - CONF
AU  - Elek, Milica
AU  - Frank, Annika
AU  - Đoković, Nemanja
AU  - Oljačić, Slavica
AU  - Živković, Aleksandra
AU  - Nikolić, Katarina
AU  - Stark, Holger
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4861
AB  - Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like
receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl
moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety
displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to
hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds
with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity
and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity
in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In
silico examination determined high values of coefficient of determination (R2) and Spearman correlation
coefficient revealed good correlation between in silico parameters and experimentally obtained Ki values.
These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations
that has to be further investigated and could serve as novel substituent in numerous compound classes.
PB  - Mu.Ta.Lig COST ACTION CA15135
PB  - Paul Ehrlich Euro-PhD Network
C3  - BOOK of ABSTRACTS MedChem19 Catanzaro
T1  - The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands
SP  - 66
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4861
ER  - 

@conference{
author = "Elek, Milica and Frank, Annika and Đoković, Nemanja and Oljačić, Slavica and Živković, Aleksandra and Nikolić, Katarina and Stark, Holger",
year = "2019",
abstract = "Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like
receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl
moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety
displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to
hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds
with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity
and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity
in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In
silico examination determined high values of coefficient of determination (R2) and Spearman correlation
coefficient revealed good correlation between in silico parameters and experimentally obtained Ki values.
These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations
that has to be further investigated and could serve as novel substituent in numerous compound classes.",
publisher = "Mu.Ta.Lig COST ACTION CA15135, Paul Ehrlich Euro-PhD Network",
journal = "BOOK of ABSTRACTS MedChem19 Catanzaro",
title = "The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands",
pages = "66-66",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4861"
}

Elek, M., Frank, A., Đoković, N., Oljačić, S., Živković, A., Nikolić, K.,& Stark, H.. (2019). The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands. in BOOK of ABSTRACTS MedChem19 Catanzaro
Mu.Ta.Lig COST ACTION CA15135., 66-66.
https://hdl.handle.net/21.15107/rcub_farfar_4861

Elek M, Frank A, Đoković N, Oljačić S, Živković A, Nikolić K, Stark H. The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands. in BOOK of ABSTRACTS MedChem19 Catanzaro. 2019;:66-66.
https://hdl.handle.net/21.15107/rcub_farfar_4861 .

Elek, Milica, Frank, Annika, Đoković, Nemanja, Oljačić, Slavica, Živković, Aleksandra, Nikolić, Katarina, Stark, Holger, "The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands" in BOOK of ABSTRACTS MedChem19 Catanzaro (2019):66-66,
https://hdl.handle.net/21.15107/rcub_farfar_4861 .