Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
Juan C. Garro Martinez, Esteban G. Vega-Hissi, Matias F. Andrada, Pablo R. Duchowicz, Francisco Torrens and Mario R. Estrada
Affiliation: Area de Quimica Física, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, San Luis, 5700, Argentina.
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.
Keywords: Anticonvulsant activity, carbonic anhydrase, dragon descriptors, lacosamide derivatives, molecular docking,
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