Antidepressant and Computational Study of Benzothiazole Incorporated Barbituric Acid Derivatives

Most currently marketed antidepressants demand the development of newer compounds due to their numerous adverse side effects. In recent years, benzothiazole derivatives have have gained prominence due to their extensive range of biological activities. The objective of the present research is to discover potent lead molecules which can be of use for future antidepressant studies. The antidepressant activity of our previously synthesized benzothiazole-incorporated barbituric acid derivatives (4a-t) was evaluated in albino mice using the forced swimming test (FST). The rotarod test was used to determine the level of minimum motor impairment in mice. The most effective compounds in the series, according to the statistical analysis of the data, were 4b, 4g, and 4l (p< 0.01). The docking analysis showed that the drugs interact with hydrogen bonding and pi-pi with docking score (in kcal/mol) of 4.686 to -3.639 with the 5HT1A receptor. The high potency of the compounds can expedite the development of new clinical entities to be promising antidepressants. These compounds appear worthy of further exploration in other models for elucidating their mechanism of action at the molecular level.