New 2-arylnaphthalenediols and triol inhibitors of HIV-1 integrase--discovery of a new polyhydroxylated antiviral agent.
A series of 13 hydroxylated 2-arylnaphthalenes have been synthesized and evaluated as HIV-1 integrase inhibitors. 7-(3,4,5-trihydroxyphenyl)naphthalene-1,2,3-triol 1c revealed chemical instability upon storage, leading to the isolation of a dimer 5c which was also tested. In the 2-arylnaphthalene series, all compounds were active against HIV-1 IN with IC50's within the 1-10 microM range, except for 1c and 5c which displayed submicromolar activity. Antiviral activity against HIV-1 replication was measured on 1b-c and 5c. Amongst the tested molecules, only 5c was found to present antiviral properties with a low cytotoxicity on two different cell lines.
Maurin
Cédric
C
Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Lion
Cédric
C
Bailly
Fabrice
F
Touati
Nadia
N
Vezin
Hervé
H
Mbemba
Gladys
G
Mouscadet
Jean François
JF
Debyser
Zeger
Z
Witvrouw
Myriam
M
Cotelle
Philippe
P
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D009281:Naphthalenes