Anti-Helicobacter pylori activity of ethoxzolamide

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 34; no. 1; pp. 1660 - 1667
• Main Authors: Modak, Joyanta K., Tikhomirova, Alexandra, Gorrell, Rebecca J., Rahman, Mohammad M., Kotsanas, Despina, Korman, Tony M., Garcia-Bustos, Jose, Kwok, Terry, Ferrero, Richard L., Supuran, Claudiu T., Roujeinikova, Anna
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2019; Taylor & Francis Group
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Dose-Response Relationship, Drug; ethoxzolamide; Ethoxzolamide - chemical synthesis; Ethoxzolamide - chemistry; Ethoxzolamide - pharmacology; genome sequencing; Helicobacter pylori - drug effects; Helicobacter pylori - growth & development; MIC/MBC; Microbial Sensitivity Tests; Molecular Structure; Mutation frequency; Research Paper; Structure-Activity Relationship; genome sequencing; ethoxzolamide; Mutation frequency; MIC/MBC
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2019.1663416

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 × 10 −9 , showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.