Thymoanaleptic Properties of Novel Synthesized Heterocyclic Derivatives of α-cyanothioacetamide

BACKGROUND: Antidepressants are associated with various adverse effects, largely due to their broad activity profiles involving central and peripheral biological targets. AIM: To investigate the thymoanaleptic effects of novel synthesized α-cyanothioacetamide derivatives using Porsolt’s forced swim test. MATERIAL AND METHODS: Among 340 synthesized compounds, in silico biological screening identified 8 with potential antidepressant activity. Porsolt’s forced swim test was conducted in 110 outbred white rats divided into 11 groups: the control group; comparison group 1 (amitriptyline, 5 mg/kg); comparison group 2 (fluoxetine, 5 mg/kg); and eight experimental groups (test compounds, 5 mg/kg). Statistical analysis was performed using Microsoft Excel 2019, an online calculator for statistical testing, and Statistica 10.0. Data homogeneity and significance were assessed using the coefficient of variation and the Wilcoxon T test. RESULTS: Compounds d02-20, AZ-127, and AZ-128 significantly reduced the immobility time and increased the swimming and jumping behaviors compared with the control group. The compounds showed greater efficacy in jumping activity than amitriptyline and fluoxetine. No significant differences in swimming or immobility indicators were found between the experimental groups and those treated with the reference drugs. CONCLUSION: The tested α-cyanothioacetamide derivatives indicated thymoanaleptic activity in Porsolt’s forced swim test in rats.