Open AccessSynthesis of Novel Benzazole Derivatives and Evaluation of Their Antidepressant-Like Activities with Possible Underlying Mechanisms
Author(s) -
Gamze Tokgöz,
Ümide Demir Özkay,
Derya Osmani̇ye,
Nazlı Turan Yücel,
Özgür Devrim Can,
Zafer Asım Kaplancıklı
Publication year - 2018
Publication title -
molecules/molecules online/molecules annual
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 149
eISSN - 1433-1373
pISSN - 1420-3049
DOI - 10.3390/molecules23112881
Subject(s) - ketanserin , antagonist , chemistry , serotonergic , behavioural despair test , tail suspension test , antidepressant , pharmacology , ritanserin , serotonin , stereochemistry , 5 ht receptor , receptor , medicine , biochemistry , hippocampus
Novel benzazole derivative compounds 4a ⁻ 4h were obtained by the reaction of corresponding 2-(benzazol-2-ylthio)acetohydrazide and appropriate 4-substituted benzaldehydes. The chemical structures of the synthesized compounds were elucidated by FT-IR, ¹H-NMR, 13 C-NMR and LCMS spectroscopic methods. Antidepressant-like effects of the compounds were evaluated by tail suspension test (TST) and modified forced swimming tests (MFST). Moreover, locomotor activities of the animals were assessed by an activity cage apparatus. In the series, compounds 4a , 4b , 4e and 4f (at 50 mg/kg) significantly decreased the immobility time of mice in both of the TST and MFST. The same compounds prolonged the swimming time of animals in MFST without any change in the climbing duration. These data indicated that compounds 4a , 4b , 4e and 4f possess significant antidepressant-like activities. Moreover, pre-treatments with p -chloro-phenylalanine methyl ester (an inhibitor of serotonin synthesis), NAN-190 (a 5-HT 1A antagonist), ketanserin (a 5-HT 2A/2C antagonist), and ondansetron (a 5-HT₃ antagonist) reversed the exhibited pharmacological effects. Results of the mechanistic studies suggested the involvement of serotonergic system and contributions of 5-HT 1A , 5-HT 2A/2C and 5-HT₃ receptors to the antidepressant-like effects of compounds 4a , 4b , 4e and 4f . Furthermore, unchanged locomotor activity of mice following the administrations of these four derivatives confirmed that the presented antidepressant-like effects are specific.