QSAR development to describe HIV-1 integrase inhibition

HIV-1 integrase(IN) is one of three viral enzymes required for replication. IN mediates integration of viral DNA into the host genome in two steps: 3' -processing and strand transfer. It is currently recognized as an important target for therapeutic development against AIDS. QSAR (Quantitative Struct ure-Activity Relationship) modeling was utilized to study HIV-1 integrase i nhibition. QSAR models were constructed to predict the IC50 values for the two structural classes (salicyhydrazines and tyrphostins) independently and in combination. The results showed that the models for different structura l classes have different dependence on the same descriptors. It suggests th at salicylhydrazines and tyrphostins might have different binding sites in HIV-1 integrase. (C) 2000 Elsevier Science B.V. All rights reserved.