New 2-arylnaphthalenediols and triol inhibitors of HIV-1 integrase—Discovery of a new polyhydroxylated antiviral agent

A series of 13 hydroxylated 2-arylnaphthalenes has been synthesized and evaluated as HIV-1 integrase inhibitors. 7-(3,4,5-Trihydroxyphenyl)naphthalene-1,2,3-triol was converted to a dimer. This dimer displays submicromolar activity against HIV-1 IN and was found to present antiviral properties with a low cytotoxicity on two different cell lines. 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 1–10μM 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.