6-Aminoquinolones as new potential anti-HIV agents.
A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC(50) value was 0.1 microM, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.
Cecchetti
V
V
Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Parolin
C
C
Moro
S
S
Pecere
T
T
Filipponi
E
E
Calistri
A
A
Tabarrini
O
O
Gatto
B
B
Palumbo
M
M
Fravolini
A
A
Palu'
G
G
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014709:Vero Cells
C415185:6-amino-1,4-dihydro-1-methyl-7-(4-(2-pyridyl)piperazin-1-yl)-4-oxo-1H-quinoline-3-carboxylic acid; D019380:Anti-HIV Agents; D004279:DNA, Viral; D010879:Piperazines; D015363:Quinolones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors