Computer-Assisted Identification of Protective Effect of Natural and Artificial Non-nutritive Sweeteners in the Maximal Electroshock Seizure (MES) Test.

ALAN TALEVI; MARÍA ELENA DEL VALLE; ANDREA V. ENRIQUE; MARÍA A. ROSELLA; MAURICIO E. DI IANNI; FIORELLA BRUNO; LUIS E. BRUNO-BLANCH

Valparaíso

Encuentro; Latin American Zebrafish Network Meeting; 2014

Universidad de Valparaíso

Epilepsy is the most frequent chronic condition affecting the Central Nervous System. Currently available medication fails to control the symptoms in around one third of the patients, which justifies the ongoing research on novel antiepileptic therapies (World Health Organization, Fact sheet 999, 2012). A previously reported QSAR model capable of identifying anticonvulsant drug candidates with protective effects in the MES test (Talevi et al., J. Comput. Aided Mol. Des. 2007) indicated that a number of artificial sweeteners (among the saccharin, cyclamate and acesulfame) might have anticonvulsant effects. After validating those predictions in the MES test, bioinformatic tools were applied to propose a structural connection between known molecular targets of epilepsy (metabotropic glutamate receptors subtypes 1 and 5) (Talevi et al., Bioorg. Med. Chem. Lett. 2012) and the sweet taste receptor. subsequently, computational models were applied to predict whether constituents from Stevia rebaudiana (a plant native to South America that has recently been approved for use as a sweetener by the Joint Food and Agriculture Organization) might have anticonvulsant properties. Our computational models predicted protective effects for several metabolites of the steviosides. Preclinical testing of a stevia aqueous infusion and isolated constituents in the MES test corroborated our predictions. Our results can be regarded as a successful case of systematic drug repositioning with a focus on food additives.