130733 20240131210810.0 doi 10.1021/jm400786q sideral 82625 ART-2013-82625 eng Galano, J. J. Universidad de Zaragoza (orcid)0000-0002-1896-7805 Improved flavodoxin inhibitors with potential therapeutic effects against Helicobacter pylori infection 2013 Helicobacter 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. Access copy available to the general public Unrestricted info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 5.48 2013 CHEMISTRY, MEDICINAL 3 / 58 = 0.052 2013 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Alías, M. (orcid)0000-0001-9018-4381 Pérez, R. (orcid)0000-0001-6775-1712 Velázquez-Campoy, A. Universidad de Zaragoza (orcid)0000-0001-5702-4538 Hoffman, P. S. Sancho, J. Universidad de Zaragoza (orcid)0000-0002-2879-9200 1002 X Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Proy. investigación DEA 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 56, 15 (2013), 6248-6258 J. med. chem. Journal of medicinal chemistry 0022-2623 693871 http://zaguan.unizar.es/record/130733/files/texto_completo.pdf Postprint 786439 http://zaguan.unizar.es/record/130733/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:130733 articulos driver 2024-01-31-19:16:46 ARTICLE