Cationic Amphiphiles with Specificity against Gram-Positive and Gram-Negative Bacteria: Chemical Composition and Architecture Combat Bacterial Membranes.
Anti-Bacterial Agents
/ chemical synthesis
Cations
/ chemical synthesis
Cell Membrane
/ drug effects
Cells, Cultured
Gram-Negative Bacteria
/ cytology
Gram-Positive Bacteria
/ cytology
Humans
Hydrophobic and Hydrophilic Interactions
Microbial Sensitivity Tests
Particle Size
Surface Properties
Surface-Active Agents
/ chemical synthesis
Journal
Langmuir : the ACS journal of surfaces and colloids
ISSN: 1520-5827
Titre abrégé: Langmuir
Pays: United States
ID NLM: 9882736
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
pubmed:
20
3
2019
medline:
29
7
2020
entrez:
20
3
2019
Statut:
ppublish
Résumé
Small-molecule cationic amphiphiles (CAms) were designed to combat the rapid rise in drug-resistant bacteria. CAms were designed to target and compromise the structural integrity of bacteria membranes, leading to cell rupture and death. Discrete structural features of CAms were varied, and structure-activity relationship studies were performed to guide the rational design of potent antimicrobials with desirable selectivity and cytocompatibility profiles. In particular, the effects of cationic conformational flexibility, hydrophobic domain flexibility, and hydrophobic domain architecture were evaluated. Their influence on antimicrobial efficacy in Gram-positive and Gram-negative bacteria was determined, and their safety profiles were established by assessing their impact on mammalian cells. All CAms have a potent activity against bacteria, and hydrophobic domain rigidity and branched architecture contribute to specificity. The insights gained from this project will aid in the optimization of CAm structures.
Identifiants
pubmed: 30888181
doi: 10.1021/acs.langmuir.9b00110
pmc: PMC6832706
mid: NIHMS1057123
doi:
Substances chimiques
Anti-Bacterial Agents
0
Cations
0
Surface-Active Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5557-5567Subventions
Organisme : NIAID NIH HHS
ID : R21 AI126053
Pays : United States
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