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Novel benzazole derivative compounds <b>4a</b>&#8315;<b>4h</b> 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, ¹³C-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 <b>4a</b>, <b>4b</b>, <b>4e</b> and <b>4f</b> (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 <b>4a</b>, <b>4b</b>, <b>4e</b> and <b>4f</b> possess significant antidepressant-like activities. Moreover, pre-treatments with <i>p</i>-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 <b>4a</b>, <b>4b</b>, <b>4e</b> and <b>4f</b>. Furthermore, unchanged locomotor activity of mice following the administrations of these four derivatives confirmed that the presented antidepressant-like effects are specific.