Synthesis, characterization & anticonvulsant activity of amide derivatives of 4-amino-1,2-naphthoquinone

Abstract

In the present study, 4-amino-1,2-naphthoquinone analogues were synthesized and characterized by spectroscopic (FT-IR, 1H NMR and 13C NMR) and elemental analysis. The synthesized compounds were evaluated for anticonvulsant activity by the maximal electroshock (MES) test and subcutaneous pentylenetetrazole (sc. PTZ) test, the most widely employed seizure models for early identification of anticonvulsant candidates, whereas their neurotoxicity was examined by rotarod test. Compounds were administered to animals at different concentrations (10, 20 & 40 mg/kg) by intraperitonial (i.p.) route and the % seizure protection was measured. The pharmacological results revealed that majority of compounds were effective in MES and sc. PTZ tests. Compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)butyramide (4) and N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)-3-methylbutanamide (6) were active at the dose 40 & 20 mg/kg, respectively, while compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)hexanamide (7) and 4-acetamido-N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)benzamide (10) were active at the dose 10 mg/kg and emerged as the most active compounds of the series. These compounds showed anticonvulsant effect comparable to phenytoin which was used as reference antiepileptic drug. The above-mentioned compounds have diminutive neurotoxic effects so they can move on next phase of anticonvulsant drug development.