Three-dimensional quantitative structure-activity relationship (QSAR) of HIV integrase inhibitors: a comparative molecular field analysis (CoMFA) study.
We present the results from a comparative molecular field analysis (CoMFA) of a set of flavone analogs that inhibit HIV-1 integrase-mediated cleavage (3'-processing step) and integration (strand transfer step) in vitro. The results indicate a strong correlation between the inhibitory activity of these flavones and the steric and electrostatic fields around them. CoMFA quantitative structure-activity relationship models with considerable predictive ability (cross-validated r2 as high as 0.8) were obtained.
Raghavan
K
K
Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Buolamwini
J K
JK
Fesen
M R
MR
Pommier
Y
Y
Kohn
K W
KW
Weinstein
J N
JN
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D019426:Integrases; D016018:Least-Squares Analysis; D008958:Models, Molecular; D008968:Molecular Conformation; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
D005419:Flavonoids; D004254:DNA Nucleotidyltransferases; D019426:Integrases