000087727 001__ 87727
000087727 005__ 20230914083240.0
000087727 0247_ $$2doi$$a10.3390/pharmaceutics11120681
000087727 0248_ $$2sideral$$a115811
000087727 037__ $$aART-2019-115811
000087727 041__ $$aeng
000087727 100__ $$0(orcid)0000-0002-0531-0943$$aGonzález, Andrés$$uUniversidad de Zaragoza
000087727 245__ $$aRepurposing dihydropyridines for treatment of helicobacter pylori infection
000087727 260__ $$c2019
000087727 5060_ $$aAccess copy available to the general public$$fUnrestricted
000087727 5203_ $$aAntibiotic resistance is a major cause of the increasing failures in the current eradication therapies against Helicobacter pylori. In this scenario, repurposing drugs could be a valuable strategy to fast-track novel antimicrobial agents. In the present study, we analyzed the inhibitory capability of 1, 4-dihydropyridine (DHP) antihypertensive drugs on the essential function of the H. pylori response regulator HsrA and investigated both the in vitro antimicrobial activities and the in vivo efficacy of DHP treatments against H. pylori. Six different commercially available and highly prescribed DHP drugs—namely, Nifedipine, Nicardipine, Nisoldipine, Nimodipine, Nitrendipine, and Lercanidipine—noticeably inhibited the DNA binding activity of HsrA and exhibited potent bactericidal activities against both metronidazole-and clarithromycin-resistant strains of H. pylori, with minimal inhibitory concentration (MIC) values in the range of 4 to 32 mg/L. The dynamics of the decline in the bacterial counts at 2 × MIC appeared to be correlated with the lipophilicity of the drugs, suggesting different translocation efficiencies of DHPs across the bacterial membrane. Oral treatments with 100 mg/kg/day of marketed formulations of Nimodipine or Nitrendipine in combination with omeprazole significantly reduced the H. pylori gastric colonization in mice. The results presented here support a novel therapeutic solution for treatment of antibiotic-resistant H. pylori infections.
000087727 536__ $$9info:eu-repo/grantAgreement/ES/CI2017-001-3$$9info:eu-repo/grantAgreement/ES/DGA/B25$$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/FIS/PI11-02578$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MINECO/FJCI-2014-20704$$9info:eu-repo/grantAgreement/ES/MINECO/IJCI-2016-27419
000087727 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000087727 590__ $$a4.421$$b2019
000087727 591__ $$aPHARMACOLOGY & PHARMACY$$b44 / 270 = 0.163$$c2019$$dQ1$$eT1
000087727 592__ $$a0.894$$b2019
000087727 593__ $$aPharmaceutical Science$$c2019$$dQ1
000087727 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000087727 700__ $$aCasado, Javier
000087727 700__ $$aChueca, Eduardo
000087727 700__ $$0(orcid)0000-0003-0195-5434$$aSalillas, Sandra$$uUniversidad de Zaragoza
000087727 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000087727 700__ $$aEspinosa Angarica, Vladimir
000087727 700__ $$aBénejat, Lucie
000087727 700__ $$aGuignard, Jérome
000087727 700__ $$aGiese, Alban
000087727 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000087727 700__ $$aLehours, Philippe
000087727 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza
000087727 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000087727 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000087727 773__ $$g11, 12 (2019), 681  [18 pp.]$$pPharmaceutics$$tPharmaceutics$$x1999-4923
000087727 8564_ $$s1311995$$uhttps://zaguan.unizar.es/record/87727/files/texto_completo.pdf$$yVersión publicada
000087727 8564_ $$s497301$$uhttps://zaguan.unizar.es/record/87727/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000087727 951__ $$a2023-09-13-10:47:50
000087727 980__ $$aARTICLE