Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.
Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse transcriptases resistant to nevirapine (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at position 100 to isoleucine) are cross resistant to E-BPU analogs. Nevirapine- or TIBO R82150-resistant HIV-1 were cross resistant to E-BPU analogs but were inhibited at concentrations 11- to 135-fold lower than the cytotoxic doses.
Piras
G
G
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Dutschman
G E
GE
Im
G J
GJ
Pan
B C
BC
Chu
S H
SH
Cheng
Y C
YC
D000998:Antiviral Agents / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D019829:Nevirapine; D011725:Pyridines / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000998:Antiviral Agents; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; C093181:5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil; D014498:Uracil; D019829:Nevirapine; D054303:HIV Reverse Transcriptase