Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 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-HT1A, 5-HT...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Chemistry Central Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s13065-018-0422-5 |
| _version_ | 1818348334052540416 |
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| author | Krzysztof Marciniec Rafał Kurczab Maria Książek Ewa Bębenek Elwira Chrobak Grzegorz Satała Andrzej J. Bojarski Joachim Kusz Paweł Zajdel |
| author_facet | Krzysztof Marciniec Rafał Kurczab Maria Książek Ewa Bębenek Elwira Chrobak Grzegorz Satała Andrzej J. Bojarski Joachim Kusz Paweł Zajdel |
| author_sort | Krzysztof Marciniec |
| collection | DOAJ |
| description | 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-HT1A, 5-HT6, 5-HT7, and dopamine D2 receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-HT1A and 5-HT7 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 (τ2) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors. |
| first_indexed | 2024-12-13T17:48:24Z |
| format | Article |
| id | doaj.art-15d0490c26fd4615adc6c75587e8b1be |
| institution | Directory Open Access Journal |
| issn | 1752-153X |
| language | English |
| last_indexed | 2024-12-13T17:48:24Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Chemistry Central Journal |
| spelling | doaj.art-15d0490c26fd4615adc6c75587e8b1be2022-12-21T23:36:34ZengBMCChemistry Central Journal1752-153X2018-05-0112111210.1186/s13065-018-0422-5Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligandsKrzysztof Marciniec0Rafał Kurczab1Maria Książek2Ewa Bębenek3Elwira Chrobak4Grzegorz Satała5Andrzej J. Bojarski6Joachim Kusz7Paweł Zajdel8Department of Organic Chemistry, Medical University of SilesiaDepartment of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of SciencesInstitute of Physics, University of SilesiaDepartment of Organic Chemistry, Medical University of SilesiaDepartment of Organic Chemistry, Medical University of SilesiaDepartment of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of SciencesDepartment of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of SciencesInstitute of Physics, University of SilesiaDepartment of Medicinal Chemistry, Jagiellonian University Medical CollegeAbstract 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-HT1A, 5-HT6, 5-HT7, and dopamine D2 receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-HT1A and 5-HT7 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 (τ2) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors.http://link.springer.com/article/10.1186/s13065-018-0422-5AzinesulfonamidesLong-chain arylpiperazineAripiprazoleCrystal structureHalogen bond |
| spellingShingle | Krzysztof Marciniec Rafał Kurczab Maria Książek Ewa Bębenek Elwira Chrobak Grzegorz Satała Andrzej J. Bojarski Joachim Kusz Paweł Zajdel Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands Chemistry Central Journal Azinesulfonamides Long-chain arylpiperazine Aripiprazole Crystal structure Halogen bond |
| title | Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands |
| title_full | Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands |
| title_fullStr | Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands |
| title_full_unstemmed | Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands |
| title_short | Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands |
| title_sort | structural determinants influencing halogen bonding a case study on azinesulfonamide analogs of aripiprazole as 5 ht1a 5 ht7 and d2 receptor ligands |
| topic | Azinesulfonamides Long-chain arylpiperazine Aripiprazole Crystal structure Halogen bond |
| url | http://link.springer.com/article/10.1186/s13065-018-0422-5 |
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