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

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

24 Cites (Scopus)

Resum

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.

Idioma original	Anglès
Pàgines (de-a)	101-111
Revista	European Journal of Medicinal Chemistry
Volum	80
DOIs	https://doi.org/10.1016/j.ejmech.2014.04.027
Estat de la publicació	Publicada - 10 de juny 2014

SDG de les Nacions Unides

Aquest resultat contribueix als següents objectius de desenvolupament sostenible.

Accés al document

10.1016/j.ejmech.2014.04.027

Altres arxius i enllaços

https://www.scopus.com/pages/publications/84899103627

Com citar-ho

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

@article{3811a049ab1040b48e02fa0f6ed54d96,

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",

volume = "80",

pages = "101--111",

}

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, pàg. 101-111. https://doi.org/10.1016/j.ejmech.2014.04.027

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

UR - https://www.scopus.com/pages/publications/84899103627

U2 - 10.1016/j.ejmech.2014.04.027

DO - 10.1016/j.ejmech.2014.04.027

M3 - Article

SN - 0223-5234

VL - 80

SP - 101

EP - 111

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

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

Resum

SDG de les Nacions Unides

Accés al document

Altres arxius i enllaços

Fingerprint

Com citar-ho