Synthesis, antidepressant evaluation and docking studies of long-chain alkylnitroquipazines as serotonin transporter inhibitors.
Chem Biol Drug Des
; 81(6): 695-706, 2013 Jun.
Article
in En
| MEDLINE
| ID: mdl-23574807
ABSTRACT
Twelve alkyl analogues (1-12) of the high-affinity serotonin transporter (SERT) inhibitor 6-nitroquipazine (6-NQ) were synthesized and studied using in vitro radioligand competition binding assays to determine their binding affinity (Ki ). The putative antidepressant activity of five of the binders with the highest SERT binding affinities was studied by the forced swim and locomotor activity mouse tests. The three-dimensional (3D) structures of 8 and 9 were determined using NOE NMR technique. Flexible docking of the compounds was undertaken to illustrate the binding of the compounds in the SERT model. Our results showed that several of the 6-NQ analogues are high-affinity SERT inhibitors and indicated that the octyl (8), decyl (10) and dodecyl (12) 6-NQ analogues exhibit moderate antidepressant activity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quipazine
/
Selective Serotonin Reuptake Inhibitors
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Serotonin Plasma Membrane Transport Proteins
/
Antidepressive Agents
Limits:
Animals
Language:
En
Journal:
Chem Biol Drug Des
Journal subject:
BIOQUIMICA
/
FARMACIA
/
FARMACOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
Norway