000130419 001__ 130419 000130419 005__ 20240125162930.0 000130419 0247_ $$2doi$$a10.1021/acs.jmedchem.9b00355 000130419 0248_ $$2sideral$$a112597 000130419 037__ $$aART-2019-112597 000130419 041__ $$aeng 000130419 100__ $$0(orcid)0000-0003-0195-5434$$aSalillas, Sandra$$uUniversidad de Zaragoza 000130419 245__ $$aDesign, 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 000130419 260__ $$c2019 000130419 5060_ $$aAccess copy available to the general public$$fUnrestricted 000130419 5203_ $$aHelicobacter 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. 000130419 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/FIS/PI11-02578$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P 000130419 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000130419 590__ $$a6.205$$b2019 000130419 591__ $$aCHEMISTRY, MEDICINAL$$b3 / 61 = 0.049$$c2019$$dQ1$$eT1 000130419 592__ $$a2.093$$b2019 000130419 593__ $$aMolecular Medicine$$c2019$$dQ1 000130419 593__ $$aDrug Discovery$$c2019$$dQ1 000130419 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000130419 700__ $$0(orcid)0000-0001-9018-4381$$aAlías, Miriam 000130419 700__ $$aMichel, Valérie 000130419 700__ $$0(orcid)0000-0002-8839-6796$$aMahía, Alejandro$$uUniversidad de Zaragoza 000130419 700__ $$0(orcid)0000-0002-0111-4697$$aLucía, Ainhoa$$uUniversidad de Zaragoza 000130419 700__ $$aRodrigues, Liliana 000130419 700__ $$aBueno, Jessica 000130419 700__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, Juan José$$uUniversidad de Zaragoza 000130419 700__ $$aDe Reuse, Hilde 000130419 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza 000130419 700__ $$0(orcid)0000-0003-0062-1029$$aCarrodeguas, José Alberto$$uUniversidad de Zaragoza 000130419 700__ $$0(orcid)0000-0001-7466-3876$$aSostres, Carlos$$uUniversidad de Zaragoza 000130419 700__ $$0(orcid)0000-0002-2519-701X$$aCastillo, Javier$$uUniversidad de Zaragoza 000130419 700__ $$0(orcid)0000-0003-2076-844X$$aAínsa. José Antonio$$uUniversidad de Zaragoza 000130419 700__ $$0(orcid)0000-0001-9033-8459$$aDíaz-de-Villegas, María Dolores 000130419 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza 000130419 700__ $$aTouati, Eliette 000130419 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza 000130419 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología 000130419 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000130419 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000130419 773__ $$g62, 13 (2019), 6102-6115$$pJ. med. chem.$$tJournal of medicinal chemistry$$x0022-2623 000130419 8564_ $$s772061$$uhttps://zaguan.unizar.es/record/130419/files/texto_completo.pdf$$yPostprint 000130419 8564_ $$s1137902$$uhttps://zaguan.unizar.es/record/130419/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000130419 909CO $$ooai:zaguan.unizar.es:130419$$particulos$$pdriver 000130419 951__ $$a2024-01-25-15:09:18 000130419 980__ $$aARTICLE