117653 20240319081018.0 doi 10.3389/fmicb.2022.874709 sideral 129068 ART-2022-129068 eng González, Andrés Universidad de Zaragoza (orcid)0000-0002-0531-0943 1,4-Dihydropyridine as a Promising Scaffold for Novel Antimicrobials Against Helicobacter pylori 2022 Access copy available to the general public Unrestricted The increasing occurrence of multidrug-resistant strains of the gastric carcinogenic bacterium Helicobacter pylori threatens the efficacy of current eradication therapies. In a previous work, we found that several 1,4-dihydropyridine (DHP)-based antihypertensive drugs exhibited strong bactericidal activities against H. pylori by targeting the essential response regulator HsrA. To further evaluate the potential of 1,4-DHP as a scaffold for novel antimicrobials against H. pylori, we determined the antibacterial effects of 12 novel DHP derivatives that have previously failed to effectively block L- and T-type calcium channels. Six of these molecules exhibited potent antimicrobial activities (MIC ≤ 8 mg/L) against three different antibiotic-resistant strains of H. pylori, while at least one compound resulted as effective as metronidazole. Such antimicrobial actions appeared to be specific against Epsilonproteobacteria, since no deleterious effects were appreciated on Escherichia coli and Staphylococcus epidermidis. The new bactericidal DHP derivatives targeted the H. pylori regulator HsrA and inhibited its DNA binding activity according to both in vitro and in vivo analyses. Molecular docking predicted a potential druggable binding pocket in HsrA, which could open the door to structure-based design of novel anti-H. pylori drugs. info:eu-repo/grantAgreement/ES/DGA/B25-17R info:eu-repo/grantAgreement/ES/DGA/B25-20R info:eu-repo/grantAgreement/ES/DGA/E35-20R info:eu-repo/grantAgreement/ES/MCIU/PID2019-104889GB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.2 2022 MICROBIOLOGY 38 / 135 = 0.281 2022 Q2 T1 1.19 2022 Microbiology (medical) 2022 Q1 Microbiology 2022 Q1 7.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Casado, Javier Gündüz, Miyase Gözde Santos, Brisa Velázquez-Campoy, Adrián Universidad de Zaragoza (orcid)0000-0001-5702-4538 Sarasa-Buisan, Cristina Universidad de Zaragoza (orcid)0000-0002-1960-2672 Fillat, María F. Universidad de Zaragoza (orcid)0000-0001-8644-4574 Montes, Milagrosa Piazuelo, Elena Universidad de Zaragoza (orcid)0000-0001-5813-3445 Lanas, Ángel Universidad de Zaragoza (orcid)0000-0001-5932-2889 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 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. 13 (2022), 874709 [13 pp.] Front. microbiol. Frontiers in Microbiology 1664-302X 2667424 http://zaguan.unizar.es/record/117653/files/texto_completo.pdf Versión publicada 2425582 http://zaguan.unizar.es/record/117653/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117653 articulos driver 2024-03-18-15:51:43 ARTICLE