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Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent

[Image: see text] Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-positive and -negative bacteria, fungi, and leishmania parasite. Compou...

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Autores principales: Dube, Phelelisiwe S., Angula, Klaudia T., Legoabe, Lesetja J., Jordaan, Audrey, Boitz Zarella, Jan M., Warner, Digby F., Doggett, J. Stone, Beteck, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193574/
https://www.ncbi.nlm.nih.gov/pubmed/37214682
http://dx.doi.org/10.1021/acsomega.3c01406
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author Dube, Phelelisiwe S.
Angula, Klaudia T.
Legoabe, Lesetja J.
Jordaan, Audrey
Boitz Zarella, Jan M.
Warner, Digby F.
Doggett, J. Stone
Beteck, Richard M.
author_facet Dube, Phelelisiwe S.
Angula, Klaudia T.
Legoabe, Lesetja J.
Jordaan, Audrey
Boitz Zarella, Jan M.
Warner, Digby F.
Doggett, J. Stone
Beteck, Richard M.
author_sort Dube, Phelelisiwe S.
collection PubMed
description [Image: see text] Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-positive and -negative bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa. Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents.
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spelling pubmed-101935742023-05-19 Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent Dube, Phelelisiwe S. Angula, Klaudia T. Legoabe, Lesetja J. Jordaan, Audrey Boitz Zarella, Jan M. Warner, Digby F. Doggett, J. Stone Beteck, Richard M. ACS Omega [Image: see text] Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-positive and -negative bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa. Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents. American Chemical Society 2023-05-04 /pmc/articles/PMC10193574/ /pubmed/37214682 http://dx.doi.org/10.1021/acsomega.3c01406 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Dube, Phelelisiwe S.
Angula, Klaudia T.
Legoabe, Lesetja J.
Jordaan, Audrey
Boitz Zarella, Jan M.
Warner, Digby F.
Doggett, J. Stone
Beteck, Richard M.
Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
title Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
title_full Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
title_fullStr Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
title_full_unstemmed Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
title_short Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
title_sort quinolone-3-amidoalkanol: a new class of potent and broad-spectrum antimicrobial agent
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193574/
https://www.ncbi.nlm.nih.gov/pubmed/37214682
http://dx.doi.org/10.1021/acsomega.3c01406
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