Anti-Helicobacter pylori activity of ethoxzolamide

Joyanta K. Modak, Alexandra Tikhomirova, Rebecca J. Gorrell, Mohammad M. Rahman, Despina Kotsanas, Tony M. Korman, Jose Garcia-Bustos, Terry Kwok, Richard L. Ferrero, Claudiu T. Supuran, Anna Roujeinikova
2019 Journal of Enzyme Inhibition and Medicinal Chemistry  
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
more » ... f 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.
doi:10.1080/14756366.2019.1663416 pmid:31530039 pmcid:PMC6759998 fatcat:upx4jetx6vg7voo67yohnai5tu