title: 6-Aminoquinolones as new potential anti-HIV agents.
abstract: 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.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cecchetti
authors.forename: C
authors.initials: C
authors.lastname: Parolin
authors.forename: S
authors.initials: S
authors.lastname: Moro
authors.forename: T
authors.initials: T
authors.lastname: Pecere
authors.forename: E
authors.initials: E
authors.lastname: Filipponi
authors.forename: A
authors.initials: A
authors.lastname: Calistri
authors.forename: O
authors.initials: O
authors.lastname: Tabarrini
authors.forename: B
authors.initials: B
authors.lastname: Gatto
authors.forename: M
authors.initials: M
authors.lastname: Palumbo
authors.forename: A
authors.initials: A
authors.lastname: Fravolini
authors.forename: G
authors.initials: G
authors.lastname: Palu'
mesh_terms: 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
chemical_list: 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