A comparative study of the cis and trans isomers of two hydantoin compounds with anticonvulsant potency

Abstract

Hydantoins are a class of compounds renowned for their diverse medical applications, particularly in neurology. Phenytoin (Dilantin) is one of the most well-known hydantoins, primarily used to stabilize neuronal membranes and prevent the spread of seizure activity. Recently, our team synthesized and studied the physicochemical properties of two compounds, 3-amino-5,5′-dimethylhydantoin Schiff Bases (SB1 and SB2). We hypothesized that SB1 and SB2 possess anticonvulsant properties, with the cis forms expected to be more active than their trans forms. We conducted experiments using the maximal electroshock (MES) test and corneal kindling in mice to test this hypothesis. The results showed that the cis isomers of SB1 and SB2 exhibited more potent activity against seizure spread than their trans isomers, and this was observed at doses that did not induce a sedative effect. Furthermore, both trans and cis isomers of SB1 but not SB2 compound demonstrated the ability to suppress seizures in the corneal kindling test. Our findings suggest that the trans-cis conversion of the hydantoin compounds SB1 and SB2 is crucial for their effectiveness in preventing seizure spread in the MES test and that of SB1 in the corneal kindling mouse model.