Journal of Chemical Information and Computer Sciences · 2001 · 54 citations · 11 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsBinding Affinity PredictionEnzyme InhibitionLigand BindingMolecular ModelingMolecular Property PredictionQuantitative Structure-activity RelationshipsAntiviral Structure-activity RelationshipsBinding Affinity AssessmentComputational Structure-activity ModelingE-state DescriptorsElectrotopological State IndicesLeave-one-out Cross-validationPredictive Modeling Of BioactivityStructure-activity Relationship Modeling
Quantitative structure-activity relationships (QSAR), based on the atom level E-state indices and calculated molecular properties (log P, MR), have been developed for the affinity of a large set of TIBO derivatives against HIV-1 reverse transcriptase (HIV-1 RT) utilizing multiple linear regression techniques. A model with five descriptors, including four atom level E-state indices (carbon atoms 2, 4, 8, and 9) and calculated log P, showed good statistics both in the regression (r2 = 0.85 and s = 0.52) and leave-one-out cross-validation (q2 = 0.80 and s(PRESS) = 0.56) for the training set of 41 compounds. The statistics for the prediction of anti-HIV activity in the test set of 24 TIBO derivatives were r2 = 0.80 and s = 0.64, respectively. The model descriptors indicate the importance of lipophilic and electronic contributions toward HIV-1 RT inhibition of TIBO derivatives used in this study.
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Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives
Rudi Pauwels, Koen Andries, Jan Desmyter et al. · Nature · 1990 · 757 citations