Preclinical and in silico studies of 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methylthiourea: A promising agent for depression and anxiety.

The study investigated the anxiolytic, antidepressant, sedative/hypnotic and in silico molecular docking properties of the synthetic ephedrine-based derivative of thiourea, 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methylthiourea. Safety profile of the compound at various doses was determined in an acute toxicity test. Results showed significant anti-anxiety effects of the compound in all mice studies. In the elevated plus maze (EPM), the time spent and entries into open arms were significantly increased upon treatment with the test compound. In the light-dark (LD) box test the drug increased the time spent in the light compartment. In hole board (HB) assay, exploration of hole and rearing significantly increased. For anxiolytic activity, 20 mg/kg was determined to represent the optimal dose, while at a higher dose (i.e., 40 mg/kg), it caused significant sedation and increased sleep duration in thiopental-induced sleep test. Escape latency in the tail suspension test (TST) and in the forced swim test (FST) increased and immobility was significantly reduced upon 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methylthiourea administration. The molecular docking analysis was performed against the various protein target involved in the pathogenesis of anxiety. The molecular docking, molecular dynamic (MD) simulation and free energy calculation showed high binding affinity and stability of ligand with the 7VOD and 2C65 protein. Taken together, it is concluded from both the in vivo assays and molecular modeling studies that 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methylthiourea possesses significant anxiolytic and antidepressant activity in concomitant with a high safety profile.