TY - JOUR
T1 - Pentafluorosulfanyl-containing triclocarban analogs with potent antimicrobial activity
AU - Pujol, Eugènia
AU - Blanco-Cabra, Núria
AU - Julián, Esther
AU - Leiva, Rosana
AU - Torrents, Eduard
AU - Vázquez, Santiago
PY - 2018/11/2
Y1 - 2018/11/2
N2 - © 2018 by the authors. 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 N,N'-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.
AB - © 2018 by the authors. 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 N,N'-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.
KW - Antibacterial
KW - Gram-positive
KW - N,N'-diarylureas
KW - Pentafluorosulfanyl
KW - Staphylococcus aureus
KW - Triclocarban
UR - https://ddd.uab.cat/record/201038
U2 - https://doi.org/10.3390/molecules23112853
DO - https://doi.org/10.3390/molecules23112853
M3 - Article
C2 - 30400165
VL - 23
JO - Molecules
JF - Molecules
SN - 1420-3049
M1 - 2853
ER -