CONICET | Buscador de Institutos y Recursos Humanos

Despite the wide spectra of available antiepileptic drugs, one third of the patients still sufferfrom drug-resistant epilepsy, justifying the ongoing search of novel therapies. The anticonvulsant activityof propyl 4-hydroxybenzoate was previously identified through in silico screening. Here, Candida antarcticaB (CAL B) lipase was employed as biocatalyst for the enzymatic synthesis of a series of alkyl phenylacetateswhich, based on their molecular similarity to propylparaben, were tested in two acute micemodels of seizure (maximal electroshock seizure and subcutaneous pentylenetetrazol tests). Moleculardocking was later applied to explain the observed activities. All the synthesized compounds displayedsome degree of protective activity in the maximal electroshock seizure model, whereas none of themshowed protection against pentylenetetrazol-induced convulsions. Ethyl 4-methoxyphenylacetate andpropyl phenylacetate showed the most promising in vivo results. In consistence with the observed anticonvulsanteffects, propyl phenylacetate obtained the best predicted binding energy among the synthesizedalkyl phenylacetates.