3-Hydroxypyrimidine-2, 4-dione Derivatives as HIV ReverseTranscriptase-Associated RNase H Inhibitors: QSAR Analysisand Molecular Docking Studies

Aids, as a lethal disease, is caused by infection with the hiv virus that affects millions of people.three essential enzymes should be encoded for replication of hiv virus: protease, integraseand reverse transcriptase (rt). rt has two different activities including dna polymerase andribonuclease h (rnase h). however, all of the marketed rt inhibitors target only the dnapolymerase activity. therefore, ribonuclease h activity may serve as a new target for drugdiscovery. in the present study, a series of 3-hydroxypyrimidine-2, 4-dione derivatives as potentrt-associated rnase h inhibitors were applied to qsar analysis. two methods including multiplelinear regressions (mlr) and partial least squared based on genetic algorithm (ga-pls) wereutilized to find the relationship between the structural feathers and inhibitory activities of thesecompounds. the best multiple linear regression equation was generated by ga-pls method. acombination of 2d autocorrelations, topological, atom-centered, and geometrical descriptors wereselected by ga-pls as they had more effects on the inhibitory activity. then, the molecular dockingstudies were carried out. the results showed that the important amino acids inside the active site ofthe enzyme responsible for essential interactions were gln475, asp549, tyr501, ser515, trp534,asp493, tyr472, and gln480 which took part in hydrogen bond formation. furthermore, dockingenergy was plotted against pic50 predicted by ga-pls method. the result showed that there is agood correlation with r^2=0.71. consequently, these findings suggest that the better method, gapls, could be applied to design new compounds and predict their inhibitory activity.