000130733 001__ 130733
000130733 005__ 20240131210810.0
000130733 0247_ $$2doi$$a10.1021/jm400786q
000130733 0248_ $$2sideral$$a82625
000130733 037__ $$aART-2013-82625
000130733 041__ $$aeng
000130733 100__ $$0(orcid)0000-0002-1896-7805$$aGalano, J. J.$$uUniversidad de Zaragoza
000130733 245__ $$aImproved flavodoxin inhibitors with potential therapeutic effects against Helicobacter pylori infection
000130733 260__ $$c2013
000130733 5060_ $$aAccess copy available to the general public$$fUnrestricted
000130733 5203_ $$aHelicobacter pylori (Hp) infection affects onehalf of the human population and produces a variety of diseases from peptic ulcer to cancer. Current eradication therapies achieve modest success rates (around 70%), resistance to the antibiotics of choice is on the rise, and vaccination has not proved to be successful yet. Using an essential Hp protein, flavodoxin, as target, we identified three low-molecular-weight flavodoxin inhibitors with bactericidal anti-Hp properties. To improve their therapeutic indexes, we have now identified and tested 123 related compounds. We have first tested similar compounds available. Then we have designed, synthesized, and tested novel variants for affinity to flavodoxin, MIC for Hp, cytotoxicity, and bactericidal effect. Some are novel bactericidal inhibitors with therapeutic indexes of 9, 38 and 12, significantly higher than those of their corresponding leads. Developing novel Hp-specific antibiotics will help fighting Hp resistance and may have the advantage of not generally perturbing the bacterial flora.
000130733 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000130733 590__ $$a5.48$$b2013
000130733 591__ $$aCHEMISTRY, MEDICINAL$$b3 / 58 = 0.052$$c2013$$dQ1$$eT1
000130733 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000130733 700__ $$0(orcid)0000-0001-9018-4381$$aAlías, M.
000130733 700__ $$0(orcid)0000-0001-6775-1712$$aPérez, R.
000130733 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000130733 700__ $$aHoffman, P. S.
000130733 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, J.$$uUniversidad de Zaragoza
000130733 7102_ $$11002$$2X$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cProy. investigación DEA
000130733 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000130733 773__ $$g56, 15 (2013), 6248-6258$$pJ. med. chem.$$tJournal of medicinal chemistry$$x0022-2623
000130733 8564_ $$s693871$$uhttps://zaguan.unizar.es/record/130733/files/texto_completo.pdf$$yPostprint
000130733 8564_ $$s786439$$uhttps://zaguan.unizar.es/record/130733/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000130733 909CO $$ooai:zaguan.unizar.es:130733$$particulos$$pdriver
000130733 951__ $$a2024-01-31-19:16:46
000130733 980__ $$aARTICLE