Inhibition of human immunodeficiency virus type 1 tat-trans-activation-responsive region interaction by an antiviral quinolone derivative.
WM5, a 6-aminoquinolone derivative, binds with high affinity to the bulge of the trans-activation-responsive region (TAR), whereas it displays low binding affinity for the loop and stem regions of TAR and for random RNA and DNA sequences. Furthermore, WM5 disrupts the natural protein-nucleic acid complex with a 50% inhibitory concentration in the low micromolar range in both in vitro and in vivo assays.
Richter
Sara
S
Department of Pharmaceutical Sciences, University of Padua, 35131 Padua, Italy.
Parolin
Cristina
C
Gatto
Barbara
B
Del Vecchio
Claudia
C
Brocca-Cofano
Egidio
E
Fravolini
Arnaldo
A
Palù
Giorgio
G
Palumbo
Manlio
M
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011758:Pyrroles; D015363:Quinolones / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015696:Gene Products, tat; D007546:Isoquinolines; D011758:Pyrroles; D015363:Quinolones; D012367:RNA, Viral; C486449:WM5 compound; D054322:tat Gene Products, Human Immunodeficiency Virus; D002939:Ciprofloxacin