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

Autori

Famiglini V, La Regina G, Coluccia A, Masci D, Brancale A, Badia R, Riveira-Munoz E, Este JA, Crespan E, Brambilla A, Maga G, Catalano M, Limatola C, Formica FR, Cirilli R, Novellino E, Silvestri R.

Riferimenti

Journal of medicinal chemistry 60(15) 6528-6547, 2017

Autori CNR

CRESPAN, MAGA

Moduli

Abstract

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 (_-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.

Link all articolo

http://pubs.acs.org/doi/10.1021/acs.jmedchem.6b01906

Parole Chiave

Note

10.1021/acs.jmedchem.6b01906

Indietro


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