10.1021/acs.jmedchem.6b01906.s002
Valeria Famiglini
Valeria
Famiglini
Giuseppe La Regina
Giuseppe La
Regina
Antonio Coluccia
Antonio
Coluccia
Domiziana Masci
Domiziana
Masci
Andrea Brancale
Andrea
Brancale
Roger Badia
Roger
Badia
Eva Riveira-Muñoz
Eva
Riveira-Muñoz
José A. Esté
José A.
Esté
Emmanuele Crespan
Emmanuele
Crespan
Alessandro Brambilla
Alessandro
Brambilla
Giovanni Maga
Giovanni
Maga
Myriam Catalano
Myriam
Catalano
Cristina Limatola
Cristina
Limatola
Francesca Romana Formica
Francesca Romana
Formica
Roberto Cirilli
Roberto
Cirilli
Ettore Novellino
Ettore
Novellino
Romano Silvestri
Romano
Silvestri
Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV‑1 Agents
American Chemical Society
2017
racemic mixtures
chiral indolyarylsulfones
NNRTI
semipreparative level
EFV
alanine unit
excitotoxic insult
K 103N HIV
Chiral Indolylarylsulfone Non-Nucleoside
WT NL 4-3 strain
Transcriptase Inhibitors
enantiomer
resistance profile
chiral IASs
Compound 23
IAS derivatives
New Potent
K 103N Y 181C Y 188L
2017-06-19 00:00:00
Dataset
https://acs.figshare.com/articles/dataset/Chiral_Indolylarylsulfone_Non-Nucleoside_Reverse_Transcriptase_Inhibitors_as_New_Potent_and_Broad_Spectrum_Anti-HIV_1_Agents/5173387
We
designed and synthesized a series of chiral indolyarylsulfones (IASs)
as new HIV-1 NNRTIs. The new IASs <b>8</b>–<b>37</b> 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, <b>8</b>, <b>23</b>–<b>25</b>, <b>31</b>, and <b>33</b>, were separated at
semipreparative level into their pure enantiomers. The (<i>R</i>)-<b>8</b> enantiomer bearing the chiral (α-methylbenzyl)
was superior to the (<i>S</i>)-counterpart. IAS derivatives
bearing the (<i>S</i>) alanine unit, (<i>S</i>)-<b>23</b>, (<i>S</i>,<i>R</i>)-<b>25</b>, (<i>S</i>)-<b>31</b>, and (<i>S</i>)-<b>33</b>, were remarkably more potent than the corresponding
(<i>R</i>)-enantiomers. Compound <b>23</b> 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.