Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria
Abstract 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-resis...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41442-5 |
| _version_ | 1827711112022327296 |
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| author | Hanan Almolhim Ahmed E. M. Elhassanny Nader S. Abutaleb Abdallah S. Abdelsattar Mohamed N. Seleem Paul R. Carlier |
| author_facet | Hanan Almolhim Ahmed E. M. Elhassanny Nader S. Abutaleb Abdallah S. Abdelsattar Mohamed N. Seleem Paul R. Carlier |
| author_sort | Hanan Almolhim |
| collection | DOAJ |
| description | Abstract 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 (CC50 > 128 µg/mL). Promisingly, these compounds also show very weak growth inhibition of commensal vaginal bacteria. |
| first_indexed | 2024-03-10T17:49:11Z |
| format | Article |
| id | doaj.art-c26694101c4048b0850c76616094ccb5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:49:11Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c26694101c4048b0850c76616094ccb52023-11-20T09:25:50ZengNature PortfolioScientific Reports2045-23222023-09-0113111110.1038/s41598-023-41442-5Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteriaHanan Almolhim0Ahmed E. M. Elhassanny1Nader S. Abutaleb2Abdallah S. Abdelsattar3Mohamed N. Seleem4Paul R. Carlier5Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia TechDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia TechDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia TechDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia TechDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia TechDepartment of Chemistry and Virginia Tech Center for Drug Discovery, Virginia TechAbstract 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 (CC50 > 128 µg/mL). Promisingly, these compounds also show very weak growth inhibition of commensal vaginal bacteria.https://doi.org/10.1038/s41598-023-41442-5 |
| spellingShingle | Hanan Almolhim Ahmed E. M. Elhassanny Nader S. Abutaleb Abdallah S. Abdelsattar Mohamed N. Seleem Paul R. Carlier Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-023-41442-5 |
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