CHALCONSEMICARBAZONE: A NEW SCAFFOLD FOR ANTIEPILEPTIC DRUG DISCOVERY

Abstract

ABSTRACT During our investigation in the area of epileptic drug discovery, we have identified that the available conventional antiepileptic drugs are effective in 60-80% patients and in specific type of seizures and having various undesirable side effects. But in present time a new class aryl semicarbazone is emerged as new pharmacophore in epileptic drug discovery having broad spectrum activity. On the bases of work done in this area we have applied hybridization of pharmacophore strategy of drug design and developed a new pharmacophore. We have also designed a scheme for synthesizing such pharmacophore and performed their pharmacological screening for the protection of seizures, behavioral study and CNS activity. The compound 1-[1-(2,4-dihydroxyphenyl)-3-(2-hydroxyphenyl)allylidene]-4-(2-fluorophenyl) semicarbazide (8) emerged as the most active prototype molecule in all the models. Key words: semicarbazide, actophotometer, antiepileptic INTRODUCTION Epilepsy is a collective term that includes over 40 different types of human seizure disorders. Approximately 1% of the world population at any one time (>50 million people worldwide) is afflicted with this serious neurological disorder. Although the current drugs provide adequate seizure control in many patients, it is roughly estimated that up to 28-30% of patients are poorly treated with the available antiepileptic drugs (AEDs). Moreover, many AEDs have serious side effects and lifelong medication may be required. Hence, with all of these factors in mind, it has been suggested that the focus of epilepsy research should be directed to identifying the underlying mechanism of epileptogenesis and the subsequent “expression” of seizure activity, rather than resorting primarily to symptom control, that is, mere suppression of seizures [1-4]. In the past decade, various aryl semicarbazones have been designed that were structurally dissimilar from many common anticonvulsants containing the dicarboximide function (CONRCO), which may contribute to toxic side effects. Consistent advances in the design of novel anticonvulsant agents have been obtained through the works of Dimmock and his collegues, which included various aryl semicarbazones and (aryloxy) aryl semicarbazones. The terminal primary amino group was implicated in hydrogen bonding. Using the semicarbazone template, Pandeya and co-workers demonstrated through a series of successive works the significant anticonvulsant potential in animal epilepsy models for the