000117653 001__ 117653
000117653 005__ 20240319081018.0
000117653 0247_ $$2doi$$a10.3389/fmicb.2022.874709
000117653 0248_ $$2sideral$$a129068
000117653 037__ $$aART-2022-129068
000117653 041__ $$aeng
000117653 100__ $$0(orcid)0000-0002-0531-0943$$aGonzález, Andrés$$uUniversidad de Zaragoza
000117653 245__ $$a1,4-Dihydropyridine as a Promising Scaffold for Novel Antimicrobials Against Helicobacter pylori
000117653 260__ $$c2022
000117653 5060_ $$aAccess copy available to the general public$$fUnrestricted
000117653 5203_ $$aThe 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.
000117653 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-17R$$9info:eu-repo/grantAgreement/ES/DGA/B25-20R$$9info:eu-repo/grantAgreement/ES/DGA/E35-20R$$9info:eu-repo/grantAgreement/ES/MCIU/PID2019-104889GB-I00
000117653 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000117653 590__ $$a5.2$$b2022
000117653 592__ $$a1.19$$b2022
000117653 591__ $$aMICROBIOLOGY$$b38 / 135 = 0.281$$c2022$$dQ2$$eT1
000117653 593__ $$aMicrobiology (medical)$$c2022$$dQ1
000117653 593__ $$aMicrobiology$$c2022$$dQ1
000117653 594__ $$a7.8$$b2022
000117653 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000117653 700__ $$aCasado, Javier
000117653 700__ $$aGündüz, Miyase Gözde
000117653 700__ $$aSantos, Brisa
000117653 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000117653 700__ $$0(orcid)0000-0002-1960-2672$$aSarasa-Buisan, Cristina$$uUniversidad de Zaragoza
000117653 700__ $$0(orcid)0000-0001-8644-4574$$aFillat, María F.$$uUniversidad de Zaragoza
000117653 700__ $$aMontes, Milagrosa
000117653 700__ $$0(orcid)0000-0001-5813-3445$$aPiazuelo, Elena$$uUniversidad de Zaragoza
000117653 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza
000117653 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000117653 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000117653 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000117653 773__ $$g13 (2022), 874709 [13 pp.]$$pFront. microbiol.$$tFrontiers in Microbiology$$x1664-302X
000117653 8564_ $$s2667424$$uhttps://zaguan.unizar.es/record/117653/files/texto_completo.pdf$$yVersión publicada
000117653 8564_ $$s2425582$$uhttps://zaguan.unizar.es/record/117653/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000117653 909CO $$ooai:zaguan.unizar.es:117653$$particulos$$pdriver
000117653 951__ $$a2024-03-18-15:51:43
000117653 980__ $$aARTICLE