Unknown

Dataset Information

0

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae.


ABSTRACT: Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide's Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.

SUBMITTER: Abutaleb NS 

PROVIDER: S-EPMC8667909 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of <i>Neisseria gonorrhoeae</i>.

Abutaleb Nader S NS   Elhassanny Ahmed E M AEM   Nocentini Alessio A   Hewitt Chad S CS   Elkashif Ahmed A   Cooper Bruce R BR   Supuran Claudiu T CT   Seleem Mohamed N MN   Flaherty Daniel P DP  

Journal of enzyme inhibition and medicinal chemistry 20221201 1


<i>Neisseria gonorrhoeae</i> is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC<sub>50,</sub> against a panel of <i>N. gonorrhoeae</i> isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococ  ...[more]

Similar Datasets

| S-EPMC9841583 | biostudies-literature
| S-EPMC8317129 | biostudies-literature
| S-EPMC8667944 | biostudies-literature
| S-EPMC10600328 | biostudies-literature
2023-10-21 | GSE159896 | GEO
| S-EPMC10454238 | biostudies-literature
| S-EPMC7534311 | biostudies-literature
| S-EPMC7470111 | biostudies-literature
| S-EPMC6161604 | biostudies-literature
| S-EPMC10164021 | biostudies-literature