Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-$ HT_{1A} $, 5-$ HT_{7} $, and $ D_{2} $ receptor ligands
Abstract A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically evaluated. In vitro methods are used to determine their affinity for serotonin 5-$ HT_{1A} $, 5-$ HT_{6} $, 5-$ HT_{7} $, and dopamine $ D_{2} $ receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-$ HT_{1A} $ and 5-$ HT_{7} $ receptor models are then conducted to investigate the conformational preferences of selected serotonin receptor ligands in different environments. The bent conformation of tetramethylene derivatives is found in a solid state, in dimethyl sulfoxide, and as a global energy minimum during conformational analysis in a simulated water environment. Furthermore, ligand geometry in top-scored complexes is also bent, with one torsion angle in the spacer ($ τ_{2} $) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Chemistry central journal - 12(2018), 1 vom: 11. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Marciniec, Krzysztof [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Aripiprazole |
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| Anmerkungen: |
© The Author(s) 2018 |
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| doi: |
10.1186/s13065-018-0422-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR030136067 |
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| 100 | 1 | |a Marciniec, Krzysztof |e verfasserin |0 (orcid)0000-0003-4631-2360 |4 aut | |
| 245 | 1 | 0 | |a Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-$ HT_{1A} $, 5-$ HT_{7} $, and $ D_{2} $ receptor ligands |
| 264 | 1 | |c 2018 | |
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| 337 | |a Computermedien |b c |2 rdamedia | ||
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| 500 | |a © The Author(s) 2018 | ||
| 520 | |a Abstract A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically evaluated. In vitro methods are used to determine their affinity for serotonin 5-$ HT_{1A} $, 5-$ HT_{6} $, 5-$ HT_{7} $, and dopamine $ D_{2} $ receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-$ HT_{1A} $ and 5-$ HT_{7} $ receptor models are then conducted to investigate the conformational preferences of selected serotonin receptor ligands in different environments. The bent conformation of tetramethylene derivatives is found in a solid state, in dimethyl sulfoxide, and as a global energy minimum during conformational analysis in a simulated water environment. Furthermore, ligand geometry in top-scored complexes is also bent, with one torsion angle in the spacer ($ τ_{2} $) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors. | ||
| 650 | 4 | |a Azinesulfonamides |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Long-chain arylpiperazine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Aripiprazole |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Crystal structure |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Halogen bond |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Kurczab, Rafał |4 aut | |
| 700 | 1 | |a Książek, Maria |4 aut | |
| 700 | 1 | |a Bębenek, Ewa |4 aut | |
| 700 | 1 | |a Chrobak, Elwira |4 aut | |
| 700 | 1 | |a Satała, Grzegorz |4 aut | |
| 700 | 1 | |a Bojarski, Andrzej J. |4 aut | |
| 700 | 1 | |a Kusz, Joachim |4 aut | |
| 700 | 1 | |a Zajdel, Paweł |4 aut | |
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