ABSTRACT
BACKGROUND: Mannich bases are known to be an important pharmacophore or bioactive leads in the synthesis of various potential agents that have a variety of therapeutic activities like anticancer, antipsychotic, anticonvulsant, antimalarial, anti-inflammatory, antibacterial and so forth. Thus, in the present research, conjugation of moieties like 1,5-benzoxazepines and 1,5-benzothiazepines with secondary amines like piperazine, methyl piperazine and morpholine was carried out in a Mannich base with an anticipation of good anticonvulsant activity. OBJECTIVE: Synthesis, characterization, structure activity relationship and anticonvulsant activity of the Mannich bases of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. METHODS: All the derivatives were synthesized in three steps. In the first step, substituted 4-hydroxy chalconylbenzene was synthesized by the reaction of 4-hydroxyacetophenone and substituted benzaldehyde, in the presence of potassium hydroxide. In the second step, 2,3-dihydro- 1,5- benzothiazepines and 2,3-dihydro-1,5-benzoxazepines were synthesized by the reaction of 2- thio/aminophenol with chalcones in the presence of glacial acetic acid. In the third step, these compounds finally underwent Mannich reaction with different secondary amines to the respective title compounds. All the synthesized derivatives were characterised and evaluated for anticonvulsant activity using MES (Maximal Electroshock Induced Seizure) and INH (Isoniazide Induced Convulsion) models. RESULTS: The synthesized derivatives were found to be more active in the MES model than INH model, with phenytoin and diazepam being the standards respectively. Accordingly, the mode of action of the synthesized compounds may be similar to phenytoin. The methyl piperazine containing compound, at a dose of 30 mg/kg., was found to be the most active and promising compound in the series. CONCLUSION: The benzothiazepine derivatives showed better anticonvulsant activity than the benzoxazepines derivatives.
Subject(s)
Anticonvulsants/chemical synthesis , Anticonvulsants/therapeutic use , Mannich Bases/chemical synthesis , Mannich Bases/therapeutic use , Seizures/drug therapy , Animals , Drug Evaluation, Preclinical/methods , Electroshock/adverse effects , Male , Mice , Seizures/etiology , Structure-Activity RelationshipABSTRACT
A simple, specific, accurate, precise and robust high-performance thin-layer chromatographic method has been developed and validated for estimation of Lawsone in Trichup herbal hair powder (coded as a THHP), polyherbal formulation. The chromatographic development was carried out on aluminum plates pre-coated with silica gel 60F254 and good resolution was achieved with Toluene: Ethyl acetate: Glacial acetic acid (8:1:1 v/v/v) as mobile phase. Lawsone detection was carried out densitometrically at 277 nm and obtained retardation factor value was 0.46 ± 0.02. The method was validated with respect to specificity, linearity, accuracy, precision and robustness. The calibration curve was achieved to be linear over a range of 5-60 µg/ml and regression coefficient was obtained 0.998. Accuracy of chromatographic method was evaluated by standard addition method; recovery was obtained 99.25 ± 0.61%. The peak purity of Lawsone was achieved 0.999 r. Relative standard deviation for intraday and inter-day precision was 0.37-0.56% and 0.42-0.55%, respectively. The limit of detection and limit of quantification of the Lawsone were found to be 1.08 µg/m land 3.28 µg/ml, respectively. This result shows that the method was well validated. In the present study, the Lawsone content was found 0.322 ± 0.014% in THHP. This study reveals that the proposed high performance thin layer chromatography method is accurate, fast and cost- effective for routine estimation of Lawsone in polyherbal formulation.
