Synthesis and Evaluation of Hydrazone Derivatives Using N-Malonyl 1,4 Dihydropyridine as a Specific Carrier in Chemical Drug Delivery System to CNS

Abstract

A group of hydrazone derivatives were synthesized using N-malonyl-1, 4-dihydropyridine as a carrier for site specific and sustained drug delivery of the drug to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydropyridine ring. Present research is on delivering of the simple synthesized MAOIs into the brain and hence minimizing the side effects and increase the therapeutic efficacy and index of the compounds. These carrier systems were synthesized by treating a group of different acetophenones with isoniazid to form Schiff base which on treatment with 2-bromo dimethyl malonate forms novel quaternary pyridinium derivatives, reduction of which with sodium dithionite afforded a novel group of chemical delivery systems (CDSs). Moreover, the synthesized compounds were screened for their anti-depressant activity using swim despair behavioral test compared to moclobemide as a refrence at a dose of 30mg/kg. Among all the synthesized compounds, DVS-1, DVS-3, DVS-5 produced a remarkable anti-depressant activity whereas others where having moderate activity when compared to that of standard. Keywords: N-malonyl-1, 4-dihydropyridine, Hydrazone, Antidepressant