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Título:	Toxicity and efficacy evaluation of novel compounds targeting an essential protein of Helicobacter pylori
Autor:	Salillas, Sandra; Alías, Miriam CSIC; Díaz de Villegas, María D. CSIC ORCID; Sancho, Javier CSIC ORCID
Fecha de publicación:	2016
Citación:	BIFI 2016
Resumen:	Helicobacter pylori, Hp, which has become the most common bacterial infection worldwide, is specialised in the lifelong colonization of the human gastric mucosa, thus affecting nearly half of the world's population. Therefore, it has been proposed to be involved in the pathogenesis of diseases such as gastritis, peptic ulcer or gastric cancer and even, cardiovascular, hepatic or neurodegenerative disorders. Conventional therapy to treat this infection accomplishes middling success rates due to increases in resistance of the bacterium to antibiotics, so new therapeutics, which do not generally perturb the bacterial flora, are required. For this reason, many essential Hp proteins have been identified as specific targets, one of them being its redox protein flavodoxin, Hp-Fld. To develop selective antimicrobials, we follow the hypothesis that certain organic molecules could interact with a distinct pocket created in the Hp-Fld, near the cofactor binding site, interfering with flavodoxin function. This hollow is characteristic of Helicobacter pylori flavodoxin, since other similar proteins do not bear it. Accordingly, we have recently synthesized new potential compounds based on three flavodoxin inhibitors identified in a previous study. All of them are less toxic toward HeLa cells than the original lead molecules, in consonance with XTT method. These results, together with the ones from in vitro efficacy assays, have allowed us to determine the therapeutic indexes for these novel compounds. Preliminary results show that two of them stand out among the others due to their promising anti-Hp activity. Efficacy and toxicity tests are currently being undertaken in drug-resistant strains of Hp and in mice. Attending to the results of all these trials, the antibiotic effect of these new compounds toward Helicobacter pylori will be established and, ultimately, toward different diseases derived from Hp infection.
Descripción:	Resumen del póster presentado a la VII International Conference on Molecular Recognition, celebrada en Zaragoza (España) del 1 al 3 de febrero de 2016.-- et al.
URI:	http://hdl.handle.net/10261/156176
Aparece en las colecciones:	(ISQCH) Comunicaciones congresos