Design, synthesis, and docking study of benzothiazole derivatives containing isatin-Schiff base as antidepressant agents

Background and purpose: Benzothiazole and isatin heterocycles are vital scaffolds in medicinal chemistry research because of their wide-ranging pharmacological properties, especially antidepressant activity. Building on this potential, we synthesized novel compounds by combining these two active pharmacophores and evaluated them for their antidepressant properties. Experimental approach: The compounds were obtained through a two-step synthesis. Isatin-Schiff-base derivatives were prepared by refluxing isatin with appropriate hydrazide derivatives or aniline in ethanol. The final compounds were obtained as a result of reactions between appropriate isatin-Schiff-base derivatives and N-(benzothiazol-2-yl)-2-chloroacetamide in dimethylformamide. Compounds were evaluated by the forced swimming test and marble burying test after the locomotor activity assay. The monoamine oxidase enzymes were selected for docking. Findings/Results: On average, in the total number of activities during the locomotor test, there were no significant changes observed with any of the compounds compared to the control. Compounds 8b, 8d, 9, 10a , and 10c in both doses (10 and 30 mg/kg), and 10d in the high dose, decreased the count of marbles hidden compared to the control. Compounds 8b, 9 , 10b , and 10c showed a considerable reduction in immobility time in the lower dose during the forced swimming test compared to the control group. Hydrogen bond interactions were observed between compounds 8b, 8c , 9 , 10b , and 10c and the enzyme’s active site. Conclusion and implications: Compounds 9 , 10b , and 10c were identified as effective antidepressant agents in this study according to docking and experimental results.