Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands

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-...

Full description

Saved in:
Bibliographic Details
Published in:BMC chemistry 2018-05, Vol.12 (1), p.1-12, Article 55
Main Authors: Marciniec, Krzysztof, Kurczab, Rafał, Książek, Maria, Bębenek, Ewa, Chrobak, Elwira, Satała, Grzegorz, Bojarski, Andrzej J., Kusz, Joachim, Zajdel, Paweł
Format: Article
Language:English
Subjects:
Aripiprazole
Azinesulfonamides
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Computer simulation
Conformational analysis
Coordination compounds
Crystal structure
Derivatives
Dimethyl sulfoxide
Dopamine
Halogen bond
In vitro methods and tests
Ligands
Long-chain arylpiperazine
Molecular chains
Molecular docking
NMR
Nuclear magnetic resonance
Organic and Medicinal Chemistry
Receptors
Research Article
Serotonin
Sulfonamides
Two dimensional analysis
X ray analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1752-153X
1752-153X
2661-801X
DOI:10.1186/s13065-018-0422-5