Anti-Helicobacter pylori activity of ethoxzolamide

Autor:	Jose F. Garcia-Bustos, Rebecca J. Gorrell, Alexandra Tikhomirova, Terry Kwok, Despina Kotsanas, Anna Roujeinikova, Joyanta K. Modak, Richard L. Ferrero, Tony M. Korman, Mohammad M. Rahman, Claudiu T. Supuran
Rok vydání:	2019
Předmět:	Glaucoma Microbial Sensitivity Tests Pharmacology 01 natural sciences Structure-Activity Relationship Drug Discovery Medicine Mutation frequency ethoxzolamide Methazolamide Dose-Response Relationship Drug Helicobacter pylori Molecular Structure biology Ethoxzolamide 010405 organic chemistry business.industry lcsh:RM1-950 General Medicine biology.organism_classification medicine.disease mic/mbc mutation frequency Anti-Bacterial Agents 0104 chemical sciences genome sequencing 010404 medicinal & biomolecular chemistry lcsh:Therapeutics. Pharmacology business Acetazolamide Research Paper medicine.drug
Zdroj:	Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 34, Iss 1, Pp 1660-1667 (2019) Journal of Enzyme Inhibition and Medicinal Chemistry
ISSN:	1475-6374 1475-6366
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1bc4fcf670ab2a5d192fe53c2a768a7 https://doi.org/10.1080/14756366.2019.1663416 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.