Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor
Authors
Penjišević, JelenaAndrić, Deana
Šukalović, Vladimir
Roglić, Goran
Šoškić, Vukić
Kostić-Rajačić, Slađana
Article (Published version)
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A total of 14 novel arylpiperazines were synthesized, and pharmaco-logically evaluated by measuring their affinities towards the D2 dopamine receptor (DRD2) in a [3H]spiperone competition assay. All the herein described compounds consist of a benzimidazole moiety connected to N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on the DRD2–arylpiperazine complexes with the objective of exploring the receptor–ligand interactions and properties of the receptor binding site. The recently published crystal structure of DRD2 was used throughout this study. The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of DRD2 and therefore should contain a linker of 5 or 6 methylene groups long.
Keywords:
Arylpiperazines / Molecular docking / Molecular dynamics / Receptor binding siteSource:
Journal of the Serbian Chemical Society, 2019, 84, 9, 925-934Publisher:
- Beograd : Srpsko hemijsko društvo
Funding / projects:
DOI: 10.2298/JSC181029104P
ISSN: 0352-5139
WoS: 000489023300001
Scopus: 2-s2.0-85073035002
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Penjišević, Jelena AU - Andrić, Deana AU - Šukalović, Vladimir AU - Roglić, Goran AU - Šoškić, Vukić AU - Kostić-Rajačić, Slađana PY - 2019 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3661 AB - A total of 14 novel arylpiperazines were synthesized, and pharmaco-logically evaluated by measuring their affinities towards the D2 dopamine receptor (DRD2) in a [3H]spiperone competition assay. All the herein described compounds consist of a benzimidazole moiety connected to N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on the DRD2–arylpiperazine complexes with the objective of exploring the receptor–ligand interactions and properties of the receptor binding site. The recently published crystal structure of DRD2 was used throughout this study. The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of DRD2 and therefore should contain a linker of 5 or 6 methylene groups long. PB - Beograd : Srpsko hemijsko društvo T2 - Journal of the Serbian Chemical Society T1 - Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor VL - 84 IS - 9 SP - 925 EP - 934 DO - 10.2298/JSC181029104P ER -
@article{ author = "Penjišević, Jelena and Andrić, Deana and Šukalović, Vladimir and Roglić, Goran and Šoškić, Vukić and Kostić-Rajačić, Slađana", year = "2019", abstract = "A total of 14 novel arylpiperazines were synthesized, and pharmaco-logically evaluated by measuring their affinities towards the D2 dopamine receptor (DRD2) in a [3H]spiperone competition assay. All the herein described compounds consist of a benzimidazole moiety connected to N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on the DRD2–arylpiperazine complexes with the objective of exploring the receptor–ligand interactions and properties of the receptor binding site. The recently published crystal structure of DRD2 was used throughout this study. The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of DRD2 and therefore should contain a linker of 5 or 6 methylene groups long.", publisher = "Beograd : Srpsko hemijsko društvo", journal = "Journal of the Serbian Chemical Society", title = "Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor", volume = "84", number = "9", pages = "925-934", doi = "10.2298/JSC181029104P" }
Penjišević, J., Andrić, D., Šukalović, V., Roglić, G., Šoškić, V.,& Kostić-Rajačić, S.. (2019). Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society Beograd : Srpsko hemijsko društvo., 84(9), 925-934. https://doi.org/10.2298/JSC181029104P
Penjišević J, Andrić D, Šukalović V, Roglić G, Šoškić V, Kostić-Rajačić S. Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society. 2019;84(9):925-934. doi:10.2298/JSC181029104P .
Penjišević, Jelena, Andrić, Deana, Šukalović, Vladimir, Roglić, Goran, Šoškić, Vukić, Kostić-Rajačić, Slađana, "Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor" in Journal of the Serbian Chemical Society, 84, no. 9 (2019):925-934, https://doi.org/10.2298/JSC181029104P . .