Linear and nonlinear QSAR study of N-hydroxy-2-[(phenylsulfonyl)amino]acetamide derivatives as matrix metalloproteinase inhibitors.
The inhibitory activity (IC50) toward matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13) of N-hydroxy-2-[(phenylsulfonyl)amino]acetamide derivatives (HPSAAs) has been successfully modeled using 2D autocorrelation descriptors. The relevant molecular descriptors were selected by linear and nonlinear genetic algorithm (GA) feature selection using multiple linear regression (MLR) and Bayesian-regularized neural network (BRANN) approaches, respectively. The quality of the models was evaluated by means of cross-validation experiments and the best results correspond to nonlinear ones (Q2>0.7 for all models). Despite the high correlation between the studied compound IC50 values, the 2D autocorrelation space brings different descriptors for each MMP inhibition. On the basis of these results, these models contain useful molecular information about the ligand specificity for MMP S'1, S1, and S'2 pockets.
Fernández
Michael
M
Molecular Modeling Group, Center for Biotechnological Studies, University of Matanzas, Matanzas, Cuba.
Caballero
Julio
J
Tundidor-Camba
Alain
A
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000465:Algorithms; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016014:Linear Models; D061965:Matrix Metalloproteinase Inhibitors; D008957:Models, Genetic; D015394:Molecular Structure; D016571:Neural Networks, Computer; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000081:Acetamides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D013449:Sulfonamides