title: In silico studies toward the discovery of new anti-HIV nucleoside compounds through the use of TOPS-MODE and 2D/3D connectivity indices. 2. Purine derivatives.
abstract: The TOPological Substructural MOlecular DEsign (TOPS-MODE) approach has been used to predict the anti-HIV activity in MT-4 assays (Estrada et al., 2002) of a diverse range of purine-based nucleosides. A database of 206 nucleosides has been selected from the literature and a theoretical virtual screening model has been developed. The model is able of discriminating between compounds that have anti-HIV activity and those that do not, with a good classification level of 85% in the training and 82.8% in the cross-validation series. On the basis of the information generated by the model, the correct classification of practically 80% of compounds from an external prediction set has been achieved using the theoretical model. Furthermore, the contribution of a range of molecular fragments to the pharmacological action has been calculated and this could provide a powerful tool in the design of nucleoside analogues that show activity against the HIV. Finally, a QSAR model has been developed that allows quantitative data to be obtained regarding the pharmacological potency shown by this type of compound.
authors.affiliation: Faculty of Pharmacy, Department of Organic Chemistry, University of Santiago de Compostela, Santiago de Compostela 15782, Spain. qosanti@yahoo.es
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.forename: Ernesto
authors.initials: E
authors.lastname: Estrada
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Yaquelin
authors.initials: Y
authors.lastname: Gutierrez
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D019295:Computational Biology; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D011687:Purines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D011687:Purines; C030985:purine