ABSTRACT
In the present work a series of N'-arylidene-2-(benzamido)-3-(naphthalen-2-yl)acrylohydrazides were synthesized by refluxing the intermediate 2-(benzamido)-3-(naphthalen-2-yl)acrylohydrazide with various substituted benzaldehyde in the presence of glacial acetic acid. The intermediate 2-(benzamido)-3-(naphthalen-2-yl)acrylohydrazide 2 was prepared by stirring 4-((naphthalen-2-yl)methylene)-2-phenyloxazol-5(4H)-one with hydrazine hydrate in the presence of absolute ethanol. The chemical structures of the compounds were established by IR, 1H NMR and mass spectral data. All the compounds were evaluated for anti-inflammatory (in vivo, in vitro) activity and performed docking against COX-2. The compounds 3a, 3c and 3o showed good inhibition of COX-2 in in vitro studies (0.75 µM, 0.5 µM and 0.7 µM as IC50, respectively). The compounds 3c, 3e and 3f were found to be more active than standard drug phenylbutazone at equidose. Molecular docking studies showed that compound 3 m exhibited good binding affinity against COX-2 with docking score 9.328 kcal/mol, when compared to the standard celecoxib.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Hydrazones/chemical synthesis , Hydrazones/pharmacology , Molecular Docking Simulation , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Cyclooxygenase 2/chemistry , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/chemistry , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Hydrazones/chemistry , Hydrazones/therapeutic use , Molecular Structure , Structure-Activity RelationshipABSTRACT
In the present work, new indole derivatives, i.e., 5-[N,N-di alkyl amino alkoxy] azaindole 2,3- di-one derivatives, are synthesized and characterized. These compounds were subjected to acute toxicity and then screened for antiepileptic activity on maximal electroshock seizure (MES) model in albino Wistar rats. In that study 5-[2-dimethyl amino ethoxy] Azaindole-3-hydrazone,2-one and 5-[2- dimethyl amino ethoxy] Azaindole 2-one,3-thiothiosemicarbazone(IIIa) showed good antiepileptic activity and less neurotoxicity compared to phenytoin. The purpose of the present study is to investigate the effect of 5-[2-dimethyl amino ethoxy] Indole 2,3- di one and 5-[2-dimethyl amino ethoxy] Azaindole 2-one,3-thiosemicarbazone(IIIa) derivatives on biogenic amines concentrations in rat brain after induction of seizures by MES method. The aim of study was relationship between seizure activities and altered the monoamines such as Noradrenaline (NA), Dopamine (DA), Serotonin (5-HT) in forebrain of rats in MES seizure models. In MES model, study of 5-[2-dimethyl amino ethoxy] Azaindole 3-hydrazone,2-one(Va) and 5-[2-dimethyl amino ethoxy]Azaindole 2-one,3-thiosemicarbazone(IIIa) (100 mg/kg) showed significant restoration of the decreased levels of brain monoamines such as noradrenaline, dopamine, and 5-hydroxytryptamine. Thus, this study suggests that 5-[2-Dimethyl amino ethoxy] Azaindole 3-hydrazone,2-one (V) and 5-[2-dimethyl amino ethoxy] Azaindole 2-one,3-thiosemicarbazone (IIIa) increased the monoamines on rat brain, which may decrease the susceptibility to MES-induced seizure in rats.
