Two- and three-dimensional quantitative structure-activity relationships for a series of purine nucleoside phosphorylase inhibitors.
Comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis, and hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of 52 training set inhibitors of calf spleen purine nucleoside phosphorylase (PNP). Significant cross-validated correlation coefficients (CoMFA, q(2)=0.68; CoMSIA, q(2)=0.66; and HQSAR, q(2)=0.70) were obtained, indicating the potential of the models for untested compounds. The models were then used to predict the inhibitory potency of 16 test set compounds that were not included in the training set, and the predicted values were in good agreement with the experimental results. The final QSAR models along with the information gathered from 3D contour and 2D contribution maps should be useful for the design of novel inhibitors of PNP having improved potency.
Castilho
Marcelo S
MS
Laboratório de Química Medicinal e Computacional, Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense 400, 13560-970 São Carlos-SP, Brazil.
Postigo
Matheus P
MP
de Paula
Caroline B V
CB
Montanari
Carlos A
CA
Oliva
Glaucius
G
Andricopulo
Adriano D
AD
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011683:Purine-Nucleoside Phosphorylase