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Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction

[Image: see text] Multidrug-resistant bacteria are one of the current biggest threats to public health and are responsible for most nosocomial infections. Herein, we report the efficient and facile synthesis of antibacterial agents aminoalkylphenols, derived from 5-nitrosalicyladehyde and prepared t...

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Autores principales: Rimpiläinen, Tatu, Andrade, Joana, Nunes, Alexandra, Ntungwe, Epole, Fernandes, Ana S., Vale, João R., Rodrigues, João, Gomes, João Paulo, Rijo, Patricia, Candeias, Nuno R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643621/
https://www.ncbi.nlm.nih.gov/pubmed/31458255
http://dx.doi.org/10.1021/acsomega.8b02381
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author Rimpiläinen, Tatu
Andrade, Joana
Nunes, Alexandra
Ntungwe, Epole
Fernandes, Ana S.
Vale, João R.
Rodrigues, João
Gomes, João Paulo
Rijo, Patricia
Candeias, Nuno R.
author_facet Rimpiläinen, Tatu
Andrade, Joana
Nunes, Alexandra
Ntungwe, Epole
Fernandes, Ana S.
Vale, João R.
Rodrigues, João
Gomes, João Paulo
Rijo, Patricia
Candeias, Nuno R.
author_sort Rimpiläinen, Tatu
collection PubMed
description [Image: see text] Multidrug-resistant bacteria are one of the current biggest threats to public health and are responsible for most nosocomial infections. Herein, we report the efficient and facile synthesis of antibacterial agents aminoalkylphenols, derived from 5-nitrosalicyladehyde and prepared through a Petasis borono–Mannich multicomponent reaction. Minimum inhibitory concentrations (MICs) as low as 1.23 μM for a chlorine derivative were determined for multidrug-resistant Gram-positive bacteria, namely, Staphylococcus aureus and Enterococcus faecalis, two of the main pathogens responsible for infections in a hospital environment. The most promising antibacterial agents were further tested against eight strains of four Gram-positive species in order to elucidate their antibacterial broadness. In vitro cytotoxicity assays of the most active aminoalkylphenol revealed considerably lower toxicity against mammalian cells, as concentrations one order of magnitude higher than the determined MICs were required to induce human keratinocyte cell death. The phenol moiety was verified to be important in deeming the antibacterial properties of the analyzed compounds, although no correlation between such properties and their antioxidant activity was observed. A density functional theory computational study substantiated the ability of aminoalkylphenols to serve as precursors of ortho-quinone methides.
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spelling pubmed-66436212019-08-27 Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction Rimpiläinen, Tatu Andrade, Joana Nunes, Alexandra Ntungwe, Epole Fernandes, Ana S. Vale, João R. Rodrigues, João Gomes, João Paulo Rijo, Patricia Candeias, Nuno R. ACS Omega [Image: see text] Multidrug-resistant bacteria are one of the current biggest threats to public health and are responsible for most nosocomial infections. Herein, we report the efficient and facile synthesis of antibacterial agents aminoalkylphenols, derived from 5-nitrosalicyladehyde and prepared through a Petasis borono–Mannich multicomponent reaction. Minimum inhibitory concentrations (MICs) as low as 1.23 μM for a chlorine derivative were determined for multidrug-resistant Gram-positive bacteria, namely, Staphylococcus aureus and Enterococcus faecalis, two of the main pathogens responsible for infections in a hospital environment. The most promising antibacterial agents were further tested against eight strains of four Gram-positive species in order to elucidate their antibacterial broadness. In vitro cytotoxicity assays of the most active aminoalkylphenol revealed considerably lower toxicity against mammalian cells, as concentrations one order of magnitude higher than the determined MICs were required to induce human keratinocyte cell death. The phenol moiety was verified to be important in deeming the antibacterial properties of the analyzed compounds, although no correlation between such properties and their antioxidant activity was observed. A density functional theory computational study substantiated the ability of aminoalkylphenols to serve as precursors of ortho-quinone methides. American Chemical Society 2018-11-29 /pmc/articles/PMC6643621/ /pubmed/31458255 http://dx.doi.org/10.1021/acsomega.8b02381 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Rimpiläinen, Tatu
Andrade, Joana
Nunes, Alexandra
Ntungwe, Epole
Fernandes, Ana S.
Vale, João R.
Rodrigues, João
Gomes, João Paulo
Rijo, Patricia
Candeias, Nuno R.
Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction
title Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction
title_full Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction
title_fullStr Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction
title_full_unstemmed Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction
title_short Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction
title_sort aminobenzylated 4-nitrophenols as antibacterial agents obtained from 5-nitrosalicylaldehyde through a petasis borono–mannich reaction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643621/
https://www.ncbi.nlm.nih.gov/pubmed/31458255
http://dx.doi.org/10.1021/acsomega.8b02381
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