ABSTRACT
In this study, the synthesis of twelve 3-(2-thienyl)pyrazoline derivatives are described. The structures of all compounds were confirmed by UV, IR, (1)H-NMR, mass spectral data, and microanalyses. In the pharmacological studies, antidepressant and anticonvulsant activities of these compounds have been screened. The antidepressant activities of the compounds were investigated by Porsolt's behavioral despair test (forced swimming) on albino mice and compared with tranylcypromine. Among the compounds examined, the compounds 9 and 12 showed significant antidepressant activity. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (metrazol) (scMet.) tests, neurotoxicities were determined by rotarod toxicity test on albino mice. Compound 8 was found to be protective against MES in the range of 30-300 mg/kg dose levels at four hours. None of the synthesized compounds showed neurotoxicity at 30-300 mg/kg dose levels.
Subject(s)
Anticonvulsants/chemical synthesis , Antidepressive Agents/chemical synthesis , Pyrazoles/pharmacology , Animals , Anticonvulsants/pharmacology , Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Mice , Molecular Structure , Pyrazoles/adverse effects , Pyrazoles/chemical synthesis , Seizures/drug therapy , Spectrum Analysis , Structure-Activity RelationshipABSTRACT
Twelve 1-phenyl-, 1-thiocarbamoyl- and 1-N-substituted thiocarbamoyl-3-(2-furyl)-5-phenyl/(2-furyl)-2-pyrazoline derivatives were synthesized. The chemical structures of the compounds were proved by IR, (1)H NMR, Mass spectrometric data and microanalyses. The antidepressant activities of the compounds were investigated by Porsolt's behavioural despair (forced swimming) test on albino mice. 1-N-Ethylthiocarbamoyl-3-(2-furyl)-5-phenyl-2-pyrazoline (6) and 1-N-allylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline (11) reduced 33.80-31.42% duration of immobility times at 10 mg kg(-1) dose level. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (metrazol) (scMet.) tests, neurotoxicities were determined by rotarod toxicity test on albino mice. 1,5-Diphenyl-3-(2-furyl)-2-pyrazoline (2), 1-N-allylthiocarbamoyl-3-(2-furyl)-5-phenyl-2-pyrazoline (7), 1-N-allylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline (11) and 1-N-phenylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline (12) were active at 100-300 mg kg(-1) dose levels. 1-Thiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline (4), 1-N-methylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline (9) and 1-N-ethylthiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline (10) were found protective against MES and scMet. at 30-300 mg kg(-1) dose levels.
Subject(s)
Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Antidepressive Agents/chemical synthesis , Antidepressive Agents/pharmacology , Furans/chemical synthesis , Furans/pharmacology , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Animals , Anticonvulsants/toxicity , Antidepressive Agents/toxicity , Convulsants , Electroshock , Magnetic Resonance Spectroscopy , Male , Mice , Neurotoxicity Syndromes/psychology , Pentylenetetrazole , Postural Balance/drug effects , Seizures/chemically induced , Seizures/drug therapy , Spectrophotometry, Ultraviolet , Structure-Activity Relationship , Swimming/psychologyABSTRACT
Eighteen 1-phenyl-, 1-thiocarbamoyl- and 1-N-substitutedthiocarbamoyl-3-phenyl-5-heteroaryl-2-pyrazoline derivatives were synthesized and tested for their antidepressant and anticonvulsant activities. Their chemical structures were proved by spectral and microanalysis. The antidepressant activities of the compounds were investigated by the "forced swimming test". Results showed that compounds II-a, b, c, III-1b, 1c, 4a showed activities equivalent to or higher than pargyline hydrochloride (CAS 306-07-0) and tranylcypromine sulfate (CAS 13492-01-8) that were used as reference antidepressant drugs. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES), subcutaneous metrazol (ScMet.) and rotarod toxicity tests in mice according to the phase I tests of the Antiepileptic Drug Development programme. Compounds I-a, II-a, b, c, III-1b, 2a, 2c were found protective against MES and III-1b, 1c, 2a, 2c were found protective against ScMet.
