title: Structural investigation of the naphthyridone scaffold: identification of a 1,6-naphthyridone derivative with potent and selective anti-HIV activity.
abstract: Building upon a large, previously reported series of anti-HIV 6-desfluoroquinolones endowed with a peculiar mechanism of action, the inhibition of Tat-mediated transcription, replacement of the quinolone nucleus with a naphthyridone core was shown to be very productive. In this work, the naphthyridone scaffold was investigated in depth by synthesizing various analogues. This led to the identification of NM13 as the most selective derivative obtained in MT-4 cells. It is the result of the successful combination of the 1,6-naphthyridone nucleus and the C7 benzothiazolpiperazine group, which, for the first time, not only grants potent anti-HIV activity but displays very high selectivity. Further studies aimed at a more thorough investigation of the anti-HIV profile of this new derivative are in progress.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy. oriana.tabarrini@unipg.it
authors.forename: Oriana
authors.initials: O
authors.lastname: Tabarrini
authors.forename: Serena
authors.initials: S
authors.lastname: Massari
authors.forename: Luca
authors.initials: L
authors.lastname: Sancineto
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.forename: Stefano
authors.initials: S
authors.lastname: Sabatini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manfroni
authors.forename: Violetta
authors.initials: V
authors.lastname: Cecchetti
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; C561964:NM13 compound; D009287:Naphthyridines; D015363:Quinolones