130419 20240125162930.0 doi 10.1021/acs.jmedchem.9b00355 sideral 112597 ART-2019-112597 eng Salillas, Sandra Universidad de Zaragoza (orcid)0000-0003-0195-5434 Design, synthesis, and efficacy testing of nitroethylene- and 7-nitrobenzoxadiazol-based flavodoxin inhibitors against helicobacter pylori drug-resistant clinical strains and in helicobacter pylori-infected mice 2019 Helicobacter pylori (Hp) infection is the main cause of peptic ulcer and gastric cancer. Hp eradication rates have fallen due to increasing bacterial resistance to currently used broad-spectrum antimicrobials. We have designed, synthesized, and tested redox variants of nitroethylene- and 7-nitrobenzoxadiazole-based inhibitors of the essential Hp protein flavodoxin. Derivatives of the 7-nitrobenzoxadiazole lead, carrying reduced forms of the nitro group and/or oxidized forms of a sulfur atom, display high therapeutic indexes against several reference Hp strains. These inhibitors are effective against metronidazole-, clarithromycin-, and rifampicin-resistant Hp clinical isolates. Their toxicity for mice after oral administration is low, and, when administered individually at single daily doses for 8 days in a mice model of Hp infection, they decrease significantly Hp gastric colonization rates and are able to eradicate the infection in up to 60% of the mice. These flavodoxin inhibitors constitute a novel family of Hp-specific antimicrobials that may help fight the constant increase of Hp antimicrobial-resistant strains. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/DGA/E45-17R info:eu-repo/grantAgreement/ES/FIS/PI11-02578 info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 6.205 2019 CHEMISTRY, MEDICINAL 3 / 61 = 0.049 2019 Q1 T1 2.093 2019 Molecular Medicine 2019 Q1 Drug Discovery 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Alías, Miriam (orcid)0000-0001-9018-4381 Michel, Valérie Mahía, Alejandro Universidad de Zaragoza (orcid)0000-0002-8839-6796 Lucía, Ainhoa Universidad de Zaragoza (orcid)0000-0002-0111-4697 Rodrigues, Liliana Bueno, Jessica Galano-Frutos, Juan José Universidad de Zaragoza (orcid)0000-0002-1896-7805 De Reuse, Hilde Velázquez-Campoy, Adrián Universidad de Zaragoza (orcid)0000-0001-5702-4538 Carrodeguas, José Alberto Universidad de Zaragoza (orcid)0000-0003-0062-1029 Sostres, Carlos Universidad de Zaragoza (orcid)0000-0001-7466-3876 Castillo, Javier Universidad de Zaragoza (orcid)0000-0002-2519-701X Aínsa. José Antonio Universidad de Zaragoza (orcid)0000-0003-2076-844X Díaz-de-Villegas, María Dolores (orcid)0000-0001-9033-8459 Lanas, Ángel Universidad de Zaragoza (orcid)0000-0001-5932-2889 Touati, Eliette Sancho, Javier Universidad de Zaragoza (orcid)0000-0002-2879-9200 1008 630 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Microbiología 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 62, 13 (2019), 6102-6115 J. med. chem. Journal of medicinal chemistry 0022-2623 772061 http://zaguan.unizar.es/record/130419/files/texto_completo.pdf Postprint 1137902 http://zaguan.unizar.es/record/130419/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:130419 articulos driver 2024-01-25-15:09:18 ARTICLE