A 1,8-naphthyridone derivative targets the HIV-1 Tat-mediated transcription and potently inhibits the HIV-1 replication.
The emergence of multidrug resistant HIV-1 strains and the inability of the HAART to eradicate HIV-1 virus from infected patients demand new drugs able to interfere with an alternative step of the replicative cycle. The naphthyridone 3 (HM13N), described in the present study, is a promising anti-HIV agent due to its ability to inhibit the HIV-1 Tat-mediated transcription and the potent antiviral activity observed in acutely, chronically, and latently infected cells. The absence of any tendency to select for resistance mutations in vitro adds to the potential clinical value of this type of compounds, especially as these compounds are drug-like and obey the Lipinski rules.
Massari
Serena
S
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Daelemans
Dirk
D
Barreca
Maria Letizia
ML
Knezevich
Anna
A
Sabatini
Stefano
S
Cecchetti
Violetta
V
Marcello
Alessandro
A
Pannecouque
Christophe
C
Tabarrini
Oriana
O
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D019380:Anti-HIV Agents; D009287:Naphthyridines; D054322:tat Gene Products, Human Immunodeficiency Virus