Current Computer Aided-Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

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

Author(s): 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.

Keywords: Anticonvulsant activity, carbonic anhydrase, dragon descriptors, lacosamide derivatives, molecular docking, QSAR.

Abstract:

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.

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Article Details

VOLUME: 10
ISSUE: 2
Page: [160 - 167]
Pages: 8
DOI: 10.2174/1573409910666140410123706