New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors

Valeria Famiglini; Giuseppe La Regina; Antonio Coluccia; Sveva Pelliccia; Andrea Brancale; Giovanni Maga; Emmanuele Crespan; Roger Badia; Bonaventura Clotet; José A. Esté; Roberto Cirilli; Ettore Novellino; Romano Silvestri

doi:10.1016/j.ejmech.2014.04.027

New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors

Valeria Famiglini, Giuseppe La Regina, Antonio Coluccia, Sveva Pelliccia, Andrea Brancale, Giovanni Maga, Emmanuele Crespan, Roger Badia, Bonaventura Clotet, José A. Esté, Roberto Cirilli, Ettore Novellino, Romano Silvestri

Research output: Contribution to journal › Article › Research › peer-review

18 Citations (Scopus)

Abstract

New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. © 2014 Elsevier Masson SAS. All rights reserved.

Original language	English
Pages (from-to)	101-111
Journal	European Journal of Medicinal Chemistry
Volume	80
DOIs	https://doi.org/10.1016/j.ejmech.2014.04.027
Publication status	Published - 10 Jun 2014

Keywords

AIDS
HIV-1
Indolylarylsulfone
Nonnucleoside inhibitor
Reverse transcriptase

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Famiglini, V., La Regina, G., Coluccia, A., Pelliccia, S., Brancale, A., Maga, G., Crespan, E., Badia, R., Clotet, B., Esté, J. A., Cirilli, R., Novellino, E., & Silvestri, R. (2014). New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. European Journal of Medicinal Chemistry, 80, 101-111. https://doi.org/10.1016/j.ejmech.2014.04.027

Famiglini, Valeria ; La Regina, Giuseppe ; Coluccia, Antonio ; Pelliccia, Sveva ; Brancale, Andrea ; Maga, Giovanni ; Crespan, Emmanuele ; Badia, Roger ; Clotet, Bonaventura ; Esté, José A. ; Cirilli, Roberto ; Novellino, Ettore ; Silvestri, Romano. / New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 80. pp. 101-111.

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title = "New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors",

abstract = "New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. {\textcopyright} 2014 Elsevier Masson SAS. All rights reserved.",

keywords = "AIDS, HIV-1, Indolylarylsulfone, Nonnucleoside inhibitor, Reverse transcriptase",

author = "Valeria Famiglini and {La Regina}, Giuseppe and Antonio Coluccia and Sveva Pelliccia and Andrea Brancale and Giovanni Maga and Emmanuele Crespan and Roger Badia and Bonaventura Clotet and Est{\'e}, {Jos{\'e} A.} and Roberto Cirilli and Ettore Novellino and Romano Silvestri",

year = "2014",

month = jun,

day = "10",

doi = "10.1016/j.ejmech.2014.04.027",

language = "English",

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Famiglini, V, La Regina, G, Coluccia, A, Pelliccia, S, Brancale, A, Maga, G, Crespan, E, Badia, R, Clotet, B, Esté, JA, Cirilli, R, Novellino, E & Silvestri, R 2014, 'New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors', European Journal of Medicinal Chemistry, vol. 80, pp. 101-111. https://doi.org/10.1016/j.ejmech.2014.04.027

New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. / Famiglini, Valeria; La Regina, Giuseppe; Coluccia, Antonio; Pelliccia, Sveva; Brancale, Andrea; Maga, Giovanni; Crespan, Emmanuele; Badia, Roger; Clotet, Bonaventura; Esté, José A.; Cirilli, Roberto; Novellino, Ettore; Silvestri, Romano.

In: European Journal of Medicinal Chemistry, Vol. 80, 10.06.2014, p. 101-111.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors

AU - Famiglini, Valeria

AU - La Regina, Giuseppe

AU - Coluccia, Antonio

AU - Pelliccia, Sveva

AU - Brancale, Andrea

AU - Maga, Giovanni

AU - Crespan, Emmanuele

AU - Badia, Roger

AU - Clotet, Bonaventura

AU - Esté, José A.

AU - Cirilli, Roberto

AU - Novellino, Ettore

AU - Silvestri, Romano

PY - 2014/6/10

Y1 - 2014/6/10

N2 - New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. © 2014 Elsevier Masson SAS. All rights reserved.

AB - New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. © 2014 Elsevier Masson SAS. All rights reserved.

KW - AIDS

KW - HIV-1

KW - Indolylarylsulfone

KW - Nonnucleoside inhibitor

KW - Reverse transcriptase

U2 - 10.1016/j.ejmech.2014.04.027

DO - 10.1016/j.ejmech.2014.04.027

M3 - Article

VL - 80

SP - 101

EP - 111

ER -