Lacosamide derivatives with anticonvulsant activity as carbonic anhydrase inhibitors. Molecular modeling, docking and QSAR analysis.
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.
Juan C
JC
Garro Martinez
Esteban G
EG
Vega-Hissi
Matías F
MF
Andrada
Pablo R
PR
Duchowicz
Francisco
F
Torrens
Area de Quimica Fisica, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, San Luis, 5700, Argentina. jcgarro@unsl.edu.ar.
Mario R
MR
Estrada
D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology*; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000078334:Lacosamide; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship
D000081:Acetamides; D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D000078334:Lacosamide; D002256:Carbonic Anhydrases