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Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2024 Jul; Vol. 148, pp. 107451. Date of Electronic Publication: 2024 May 13. - Publication Year :
- 2024
-
Abstract
- Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Structure-Activity Relationship
Molecular Structure
Dose-Response Relationship, Drug
Thiazoles chemistry
Thiazoles pharmacology
Thiazoles chemical synthesis
DNA, Bacterial metabolism
A549 Cells
Hemolysis drug effects
Enterococcus faecalis drug effects
Coumarins chemistry
Coumarins pharmacology
Coumarins chemical synthesis
Anti-Bacterial Agents pharmacology
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents chemical synthesis
Microbial Sensitivity Tests
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 148
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38759357
- Full Text :
- https://doi.org/10.1016/j.bioorg.2024.107451