HIV integrase inhibitors with nucleobase scaffolds: discovery of a highly potent anti-HIV agent.
HIV integrase is essential for HIV replication. However, there are currently no integrase inhibitors in clinical use for AIDS. We have discovered a conceptually new beta-diketo acid that is a powerful inhibitor of both the 3'-processing and strand transfer steps of HIV-1 integrase. The in vitro anti-HIV data of this inhibitor were remarkable as exemplified by its highly potent antiviral therapeutic efficacy against HIV(TEKI) and HIV-1(NL4)(-)(3) replication in PBMC (TI >4,000 and >10,000, respectively).
Nair
Vasu
V
The Center for Drug Discovery, Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, USA. vnair@rx.uga.edu
Chi
Guochen
G
Ptak
Roger
R
Neamati
Nouri
N
D001665:Binding Sites; D019427:HIV Integrase / Q000737:chemistry; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D006885:Hydroxybutyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C508794:4-(1,3-dibenzyl-1,2,3,4-tetrahydro-2,4-dioxopyrimidin-5-yl)-2-hydroxy-4-oxobut-2-enoic acid; D019428:HIV Integrase Inhibitors; D006885:Hydroxybutyrates; D007651:Keto Acids; D011743:Pyrimidines; D014498:Uracil; D019427:HIV Integrase