In silico design of multi-target inhibitors for C-C chemokine receptors using substructural descriptors.
Rational design of entry inhibitors is an active area for the discovery of new and effective anti-HIV agents. C-C Chemokine receptors represent key targets for the HIV entry process. Several of these proteins with features to be HIV co-receptors have not been sufficiently studied or used for the design of novel entry inhibitors. With the purpose to overcome this problem, we develop here a fragment-based approach for the design of multi-target inhibitors against four C-C chemokine receptors. This approach was focused on the construction of a multi-target QSAR discriminant model using a large and heterogeneous database of compounds and substructural descriptors for the classification and prediction of inhibitors for C-C chemokine receptors. The model correctly classified more than 89% of active and inactive compounds in both: training and prediction series. As principal advantage, this model permitted the automatic and fast extraction of fragments responsible for the inhibitory activity against the different C-C chemokine receptors under study and new molecular entities were suggested as possible versatile inhibitors for these proteins.
Department of Chemistry, Faculty of Natural Sciences, University of Oriente, 90500, Santiago de Cuba, Cuba. alejspivanovich@yahoo.es
Alejandro
A
Speck-Planche
Valeria V
VV
Kleandrova
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve
D019380:Anti-HIV Agents; D019742:Chemokines, CC