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

J Chem Inf Model. 2005 Mar-Apr;45(2):502-14. doi: 10.1021/ci049662o.

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.

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Computational Biology*
  • Databases, Factual
  • Drug Evaluation, Preclinical*
  • Molecular Structure
  • Nucleosides / chemistry*
  • Nucleosides / pharmacology*
  • Purines / chemistry*
  • Quantitative Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Nucleosides
  • Purines
  • purine