Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity
Concerns have been raised about the long-term accumulating effects of triclocarban, a polychlorinated diarylurea widely used as an antibacterial soap additive, in the environment and in human beings. Indeed, the Food and Drug Administration has recently banned it from personal care products. Herein,...
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doaj-9ab47d60bf1640e9acc2b7738956fd3a2020-11-24T22:40:08ZengMDPI AGMolecules1420-30492018-11-012311285310.3390/molecules23112853molecules23112853Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial ActivityEugènia Pujol0Núria Blanco-Cabra1Esther Julián2Rosana Leiva3Eduard Torrents4Santiago Vázquez5Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l′Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, SpainBacterial Infections and Antimicrobial Therapies, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 15-21, 08028 Barcelona, SpainDepartament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, SpainLaboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l′Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, SpainBacterial Infections and Antimicrobial Therapies, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 15-21, 08028 Barcelona, SpainLaboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l′Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, SpainConcerns have been raised about the long-term accumulating effects of triclocarban, a polychlorinated diarylurea widely used as an antibacterial soap additive, in the environment and in human beings. Indeed, the Food and Drug Administration has recently banned it from personal care products. Herein, we report the synthesis, antibacterial activity and cytotoxicity of novel <i>N</i>,<i>N</i>′-diarylureas as triclocarban analogs, designed by reducing one or more chlorine atoms of the former and/or replacing them by the novel pentafluorosulfanyl group, a new bioisostere of the trifluoromethyl group, with growing importance in drug discovery. Interestingly, some of these pentafluorosulfanyl-bearing ureas exhibited high potency, broad spectrum of antimicrobial activity against Gram-positive bacterial pathogens, and high selectivity index, while displaying a lower spontaneous mutation frequency than triclocarban. Some lines of evidence suggest a bactericidal mode of action for this family of compounds.https://www.mdpi.com/1420-3049/23/11/2853antibacterialGram-positive<i>N</i>,<i>N</i>′-diarylureaspentafluorosulfanyl<i>Staphylococcus aureus</i>triclocarban |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eugènia Pujol Núria Blanco-Cabra Esther Julián Rosana Leiva Eduard Torrents Santiago Vázquez |
spellingShingle |
Eugènia Pujol Núria Blanco-Cabra Esther Julián Rosana Leiva Eduard Torrents Santiago Vázquez Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity Molecules antibacterial Gram-positive <i>N</i>,<i>N</i>′-diarylureas pentafluorosulfanyl <i>Staphylococcus aureus</i> triclocarban |
author_facet |
Eugènia Pujol Núria Blanco-Cabra Esther Julián Rosana Leiva Eduard Torrents Santiago Vázquez |
author_sort |
Eugènia Pujol |
title |
Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity |
title_short |
Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity |
title_full |
Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity |
title_fullStr |
Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity |
title_full_unstemmed |
Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity |
title_sort |
pentafluorosulfanyl-containing triclocarban analogs with potent antimicrobial activity |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-11-01 |
description |
Concerns have been raised about the long-term accumulating effects of triclocarban, a polychlorinated diarylurea widely used as an antibacterial soap additive, in the environment and in human beings. Indeed, the Food and Drug Administration has recently banned it from personal care products. Herein, we report the synthesis, antibacterial activity and cytotoxicity of novel <i>N</i>,<i>N</i>′-diarylureas as triclocarban analogs, designed by reducing one or more chlorine atoms of the former and/or replacing them by the novel pentafluorosulfanyl group, a new bioisostere of the trifluoromethyl group, with growing importance in drug discovery. Interestingly, some of these pentafluorosulfanyl-bearing ureas exhibited high potency, broad spectrum of antimicrobial activity against Gram-positive bacterial pathogens, and high selectivity index, while displaying a lower spontaneous mutation frequency than triclocarban. Some lines of evidence suggest a bactericidal mode of action for this family of compounds. |
topic |
antibacterial Gram-positive <i>N</i>,<i>N</i>′-diarylureas pentafluorosulfanyl <i>Staphylococcus aureus</i> triclocarban |
url |
https://www.mdpi.com/1420-3049/23/11/2853 |
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