Novel TOPP descriptors in 3D-QSAR analysis of apoptosis inducing 4-aryl-4H-chromenes: comparison versus other 2D- and 3D-descriptors.
Novel 3D-descriptors using Triplets Of Pharmacophoric Points (TOPP) were evaluated in QSAR-studies on 80 apoptosis-inducing 4-aryl-4H-chromenes. A predictive QSAR model was obtained using PLS, confirmed by means of internal and external validations. Performance of the TOPP approach was compared with that of other 2D- and 3D-descriptors; statistical analysis indicates that TOPP descriptors perform best. A ranking of TOPP>GRIND>BCI 4096=ECFP>FCFP>GRID-GOLPE>>DRAGON>>>MDL 166 was achieved. Finally, in a 'consensus' analysis predictions obtained using the single methods were compared with an average approach using six out of eight methods. The use of the average is statistically superior to the single methods. Beyond it, the use of several methods can help to easily investigate the presence/absence of outliers according to the 'consensus' of the predicted values: agreement among all the methods indicates a precise prediction, whereas large differences between predicted values (for the same compounds by different methods) would demand caution when using such predictions.
Laboratory for Chemometrics and Cheminformatics, Chemistry Department, University of Perugia, Via Elce di Sotto, 10, I-06123 Perugia, Italy. simone@chemiome.chm.unipg.it
Simone
S
Sciabola
Emanuele
E
Carosati
Lourdes
L
Cucurull-Sanchez
Massimo
M
Baroni
Raimund
R
Mannhold
D000465:Algorithms; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D003627:Data Interpretation, Statistical; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D013237:Stereoisomerism
D001578:Benzopyrans