Bioactivities of a series of phosphodiesterase type 5 (PDE-5) inhibitors as modelled by MIA-QSAR.
A series of cyclic guanine derivatives, phosphodiesterase type 5 (PDE-5) inhibitors, have been modelled using an image-based approach for quantitative structure-activity relationships (MIA-QSAR). The calibration model showed to be robust with a R(2) of 0.864 using five PLS components. The predictive ability of the model was tested through leave-one-out cross-validation, giving a Q(2)(CV) of 0.605 (Q(2)(CV) improves to 0.721 after removing two outliers). An external validation set was also used to give an account for the modelling capability, and the results agreed with the ones obtained from a 3D methodology previously applied to this series of compounds. The method showed to be a potential tool for predicting new drug-like compounds, as exemplified by calculating the activities of two new proposed congeners derived from the training set.
Departamento de Química, Universidade Federal de Lavras-UFLA, Caixa Postal 3037, 37200-000 Lavras, MG, Brazil.
João E
JE
Antunes
Matheus P
MP
Freitas
Roberto
R
Rittner
D003201:Computers; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D016568:Drugs, Generic / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D058986:Phosphodiesterase 5 Inhibitors; D021281:Quantitative Structure-Activity Relationship
D016568:Drugs, Generic; D004791:Enzyme Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5