Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 9; p. 1490
• Main Authors: Demir Özkay, Ümide, Kaya, Ceren, Acar Çevik, Ulviye, Can, Özgür Devrim
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.09.2017; MDPI
• Subjects: activity cage; Adenosine; Administration, Oral; Amyotrophic lateral sclerosis; Analgesics; Animals; Anticonvulsants; antidepressant; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - chemical synthesis; Antidepressive Agents - pharmacokinetics; Behavior, Animal; Benzothiazole; Benzothiazoles - administration & dosage; Benzothiazoles - chemical synthesis; Benzothiazoles - pharmacokinetics; Chemistry; Climbing; Drug Design; Drug development; Drug dosages; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - pharmacokinetics; Hindlimb Suspension - methods; Humans; Hydrocarbons; Mental depression; Mice; Mice, Inbred BALB C; modified forced swimming test; Molecular Structure; Motor Activity - drug effects; Nervous system; Order parameters; Parkinson's disease; Pharmacology; Pharmacy; Structure-Activity Relationship; Swimming; tail suspension test; Test procedures; tail suspension test; modified forced swimming test; activity cage; benzothiazole; antidepressant
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22091490

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives - . The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds , , - reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds , , - . Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds - , some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.