We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
1,4-Dihydropyridine as a Promising Scaffold for Novel Antimicrobials Against Helicobacter pylori.
- Authors
González, Andrés; Casado, Javier; Gündüz, Miyase Gözde; Santos, Brisa; Velázquez-Campoy, Adrián; Sarasa-Buisan, Cristina; Fillat, María F.; Montes, Milagrosa; Piazuelo, Elena; Lanas, Ángel
- Abstract
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.
- Subjects
HELICOBACTER pylori; CALCIUM channels; ANTI-infective agents; STAPHYLOCOCCUS epidermidis; MOLECULAR docking; ANTIHYPERTENSIVE agents
- Publication
Frontiers in Microbiology, 2022, Vol 13, p1
- ISSN
1664-302X
- Publication type
Article
- DOI
10.3389/fmicb.2022.874709