Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

Abstract

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. 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 3c, 3d, 3f–3h 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 3c, 3d, 3f–3h. 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 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

“…Mice were located individually in a device for 4 min and interruptions of light beams to the photocells throughout horizontal and vertical behavior of the mouse were recorded by the apparatus. After each trial, the floor of the cage was cleaned with alcohol [ 26 , 27 ].…”

Solid‐Supported Materials‐Based Synthesis of 2‐Substituted Benzothiazoles: Recent Developments and Sanguine Future

“…Choi and coauthors [186] employed trityl-resin as solid support for the synthesis of a diverse array of benzothiazole derivatives (19). 2-Aminobenzothiazole (18) was immobilized on the resin followed by treatment with acid chloride derivative (21) to give resin-supported carbamic chloride (22). The resinsupported carbamic chloride (22) undergoes intramolecular cyclization followed by cleavage with the TFA to give the target compound (19) (Scheme 5).…”

“…Ravi Kumar et al [209] have reported silica-supported sodium hydrogen sulfate as a heterogeneous catalyst for the synthesis of 2-substituted benzothiazoles (19). The desired synthesis was achieved by stirring a mixture of 2-aminothiophenol ( 18) and acid chloride derivatives (21) in the presence of the catalyst, NaHSO 4 -SiO 2 (25 % wt) under solvent-free conditions at 100°C for 12 h (Scheme 26). The scope of the developed protocol was expanded on the synthesis of 2-substituted benzoxazoles and benzimidazole derivatives.…”

“…Saeed Bahadorikhalili and Ali Reza Sardarian [239] used KF-Al 2 O 3 as a solid heterogeneous base catalyst and explored it in the synthesis of 2-substituted benzothiazole derivatives (19). The reaction of 2-aminothiophenol (18) with carboxylic acid derivatives such as acid chloride (21) or anhydride (116,117) resulted in the desired product. The effect of the catalyst on the reaction outcome was investigated in different solvents ACN, THF, DMF, DMSO, toluene and Et 2 O, and also under solvent-free conditions at varying temperatures.…”

Syntheses of Benzo[d]Thiazol-2(3H)-One Derivatives and Their Antidepressant and Anticonvulsant Effects

“…Benzothiazole derivatives display a wide spectrum of pharmacologic effects, including anti-inflammatory [4], antibacterial [5], antiviral [6], antioxidant [7], and immunomodulatory properties [8]. In addition to the central nervous system (CNS)-related pharmacologic effects, benzothiazole compounds have been reported to display selective inhibitory effects against monoamine oxidase [9,10,11,12], as well as anti-Alzheimer’s disease [13] and convulsions [14]. The antidepressant effect of a series of benzothiazole derivatives has been demonstrated through animal models such as the tail suspension test (TST) and forced swimming test (FST) [15,16].…”