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

C. Maurin (1) , C. Lion (1) , F. Bailly (1) , N. Touati (1, 2) , H. Vezin (1, 2) , G. Mbemba (3) , J.F. Mouscadet (3) , Z. Debyser (4) , M. Witvrouw (4) , P. Cotelle (1)

1 UMR CNRS 8009 - Laboratoire de Chimie Organique et Macromoleculaire
2 LASIRE - Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516
3 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée
4 Molecular Medicine

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 μM 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.

Mots clés: 6-Arylnaphthalene-1; 2-diols; HIV-1 Integrase inhibitors

Domaines: Matériaux; Chimie théorique et/ou physique

C. Maurin, C. Lion, F. Bailly, N. Touati, H. Vezin, et al.. New 2-arylnaphthalenediols and triol inhibitors of HIV-1 integrase—Discovery of a new polyhydroxylated antiviral agent. Bioorganic and Medicinal Chemistry, 2010, 18, pp.5194 - 5201. ⟨10.1016/j.bmc.2010.05.059⟩. ⟨hal-00561930⟩