Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis.

GARRO MARTÍNEZ, J.C.; VEGA HISSI, E.G.; ANDRADA, M.F.; DUCHOWICZ, P.R.; TORRENS, F.; ESTRADA, M.R.

CURRENT COMPUTER-AIDED DRUG DESIGN

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2014 vol. 10 p. 160 - 167

1573-4099

Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.