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Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria

Drug-resistant Neisseria gonorrhoeae represents a major threat to public health; without new effective antibiotics, untreatable gonococcal infections loom as a real possibility. In a previous drug-repurposing study, we reported that salicylic acid had good potency against azithromycin-resistant N. g...

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Autores principales: Almolhim, Hanan, Elhassanny, Ahmed E. M., Abutaleb, Nader S., Abdelsattar, Abdallah S., Seleem, Mohamed N., Carlier, Paul R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475031/
https://www.ncbi.nlm.nih.gov/pubmed/37660222
http://dx.doi.org/10.1038/s41598-023-41442-5
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author Almolhim, Hanan
Elhassanny, Ahmed E. M.
Abutaleb, Nader S.
Abdelsattar, Abdallah S.
Seleem, Mohamed N.
Carlier, Paul R.
author_facet Almolhim, Hanan
Elhassanny, Ahmed E. M.
Abutaleb, Nader S.
Abdelsattar, Abdallah S.
Seleem, Mohamed N.
Carlier, Paul R.
author_sort Almolhim, Hanan
collection PubMed
description Drug-resistant Neisseria gonorrhoeae represents a major threat to public health; without new effective antibiotics, untreatable gonococcal infections loom as a real possibility. In a previous drug-repurposing study, we reported that salicylic acid had good potency against azithromycin-resistant N. gonorrhoeae. We now report that the anti-gonococcal activity in this scaffold is easily lost by inopportune substitution, but that select substituted naphthyl analogs (3b, 3o and 3p) have superior activity to salicylic acid itself. Furthermore, these compounds retained potency against multiple ceftriaxone- and azithromycin-resistant strains, exhibited rapid bactericidal activity against N. gonorrhoeae, and showed high tolerability to mammalian cells (CC(50) > 128 µg/mL). Promisingly, these compounds also show very weak growth inhibition of commensal vaginal bacteria.
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spelling pubmed-104750312023-09-04 Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria Almolhim, Hanan Elhassanny, Ahmed E. M. Abutaleb, Nader S. Abdelsattar, Abdallah S. Seleem, Mohamed N. Carlier, Paul R. Sci Rep Article Drug-resistant Neisseria gonorrhoeae represents a major threat to public health; without new effective antibiotics, untreatable gonococcal infections loom as a real possibility. In a previous drug-repurposing study, we reported that salicylic acid had good potency against azithromycin-resistant N. gonorrhoeae. We now report that the anti-gonococcal activity in this scaffold is easily lost by inopportune substitution, but that select substituted naphthyl analogs (3b, 3o and 3p) have superior activity to salicylic acid itself. Furthermore, these compounds retained potency against multiple ceftriaxone- and azithromycin-resistant strains, exhibited rapid bactericidal activity against N. gonorrhoeae, and showed high tolerability to mammalian cells (CC(50) > 128 µg/mL). Promisingly, these compounds also show very weak growth inhibition of commensal vaginal bacteria. Nature Publishing Group UK 2023-09-02 /pmc/articles/PMC10475031/ /pubmed/37660222 http://dx.doi.org/10.1038/s41598-023-41442-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Almolhim, Hanan
Elhassanny, Ahmed E. M.
Abutaleb, Nader S.
Abdelsattar, Abdallah S.
Seleem, Mohamed N.
Carlier, Paul R.
Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
title Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
title_full Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
title_fullStr Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
title_full_unstemmed Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
title_short Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
title_sort substituted salicylic acid analogs offer improved potency against multidrug-resistant neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475031/
https://www.ncbi.nlm.nih.gov/pubmed/37660222
http://dx.doi.org/10.1038/s41598-023-41442-5
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