QSAR studies for diarylpyrimidines against HIV-1 reverse transcriptase wild-type and mutant strains.
For the activity values against HIV-1 RT wild-type and mutant strains (L100I, Y181C and Y188N) of 34 diarylpyrimidines (DAPYs) taken from literature, multiple linear regression analysis and the crossvalidation of Leave-One-Out method are carried out against the activity values with the hydrophobicity index logP, the modified steric parameter L(Y), the Muliken charge of nitrogen atom on the right wing N(C) and the indicator index I for the substituents R(3)' and R(1) on the left wing, and four good QSAR models are established: R=0.8211(N=34), R=0.8599 (N=33), R=0.8711(N=30) and R=0.9079 (N=29) for the cases of wild type, and mutant strain forms L100I, Y181C and Y188N, respectively. Additionally, the results indicate that logP plays a vital role in the prediction of the activity of DAPYs, and the cyano group on the left wing is important for inhibiting the mutant forms L100I and Y188N.
Liang
Yong-Hong
YH
Department of Chemistry, Fudan University, Shanghai 200433, PR China.
Chen
Fen-Er
FE
D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D020125:Mutation, Missense; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
D011743:Pyrimidines