Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

Abstract

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), ¹H Nuclear Magnetic Resonance Spectroscopy (¹H-NMR), ¹³C Nuclear Magnetic Resonance Spectroscopy (¹³C-NMR) and Electronspray Ionisation Mass Spectroscopy (ESI-MS) spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST) and modified forced swimming (MFST) methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg) was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

Keywords: activity cage; modified forced swimming; tail-suspension; thiadiazole.

Figure 1

Synthesis pathway of target compounds.

Figure 2

The effects of the test compounds (2a–2h) and fluoxetine on the immobility time of the mice measured in TST. Significant differences against control group, * p < 0.05, ** p < 0.01, *** p < 0.001. Values are presented as mean ± SEM, (n = 7).

Figure 3

The effects of the test compounds (2a–2h) and fluoxetine on the immobility frequencies of the mice in MFST. Significant differences against control group, * p < 0.05, ** p < 0.01, *** p < 0.001. Values are presented as mean ± SEM, (n = 7).

Figure 4

The effects of the test compounds (2a–2h) and fluoxetine on the swimming frequencies of the mice in MFST. Significant differences against control group, * p < 0.05, ** p < 0.01, *** p < 0.001. Values are presented as mean ± SEM, (n = 7).

Figure 5

The effects of the test compounds (2a–2h) and fluoxetine on the climbing frequencies of the mice in MFST. Values are presented as mean ± SEM, (n = 7).

Figure 6

The effects of the test compounds (2a–2h) on the horizontal locomotor activities of the mice in the activity cage test. Values are presented as mean ± SEM, (n = 7).

Figure 7

The effects of the test compounds (2a–2h) on the vertical locomotor activities of the mice in the activity cage test. Values are presented as mean ± SEM, (n = 7).