Details

Autor(en) / Beteiligte

• Famiglini, Valeria
• La Regina, Giuseppe
• Coluccia, Antonio
• Masci, Domiziana
• Brancale, Andrea
• Badia, Roger
• Riveira-Muñoz, Eva
• Esté, José A
• Crespan, Emmanuele
• Brambilla, Alessandro
• Maga, Giovanni
• Catalano, Myriam
• Limatola, Cristina
• Formica, Francesca Romana
• Cirilli, Roberto
• Novellino, Ettore
• Silvestri, Romano

Titel

Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV‑1 Agents

Ist Teil von

• Journal of medicinal chemistry, 2017-08, Vol.60 (15), p.6528-6547

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8–37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N–Y181C HIV-1 strains. Six racemic mixtures, 8, 23–25, 31, and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31, and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers. Compound 23 protected hippocampal neuronal cells from the excitotoxic insult, while efavirenz (EFV) did not contrast the neurotoxic effect of glutamate. The present results highlight the chiral IASs as new NNRTIs with improved resistance profile against the mutant HIV-1 strains and reduced neurotoxic effects.