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

• Published in: Scientific reports Vol. 13; no. 1; p. 14468
• Main Authors: Almolhim, Hanan, Elhassanny, Ahmed E. M., Abutaleb, Nader S., Abdelsattar, Abdallah S., Seleem, Mohamed N., Carlier, Paul R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-09-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/154/1435; 631/154/309; 631/326/22; 639/638/309/2144; 639/638/309/2419; Acids; Antibiotics; Azithromycin; Bacteria; Bactericidal activity; Ceftriaxone; Condoms; Drug resistance; Gonorrhea; Gram-negative bacteria; Gram-positive bacteria; Humanities and Social Sciences; Mammalian cells; multidisciplinary; Multidrug resistance; Multidrug resistant organisms; Neisseria gonorrhoeae; Public health; Salicylic acid; Science; Science (multidisciplinary); Vagina
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-41442-5

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.