Antibiotic resistance has become one of the greatest health threats in the world. In this study, a charge-dispersed dimerization strategy is described for the antimicrobial peptide (AMP) mimics via a tunable cationic charge to improve the selectivity between prokaryotic microbes and eukaryotic cells. This strategy is demonstrated with a series of charge-dispersed AMP mimics based on -arylimidazolium skeletons. These -arylimidazolium AMP mimics show potent antibacterial activity against strains along with a low rate of drug resistance, good hemocompatibility, and low cytotoxicity. In addition to the elimination of planktonic bacteria, -arylimidazolium AMP mimics can also inhibit biofilm formation and destroy the established biofilm. More importantly, methicillin-resistant (MRSA)-induced lung-infected mice can be effectively treated by the intravenous administration of -arylimidazolium AMP mimic, which enable the design of -arylimidazolium AMP mimics to offer an alternative avenue to eradicate drug-resistant bacterial infection.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.2c00818 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cinnamic acid alleviates endothelial dysfunction and oxidative stress by targeting PPARδ in obesity and diabetes.
Chin Med
January 2025
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
Objective: Cinnamic acid (CA) is a bioactive compound isolated from cinnamon. It has been demonstrated to ameliorate inflammation and metabolic diseases, which are associated with endothelial dysfunction. This study was aimed to study the potential protective effects of CA against diabetes-associated endothelial dysfunction and its underlying mechanisms.
View Article and Find Full Text PDFMitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.
Int J Mol Sci
January 2025
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2.
View Article and Find Full Text PDFLaminaran potentiates cGAS-STING signaling to enhance antiviral responses.
Int Immunopharmacol
January 2025
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Department of Biomedical Science, City University of Hong Kong, Kowloon, Hong Kong, China. Electronic address:
Cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes (STING) signaling pathway, an essential element in the innate antiviral immune responses, has emerged as a key component of innate immune system to modulate type I IFNs production and response by recognizing both exogenous and endogenous DNA. Although some cGAS-STING signaling small molecule agonists have been developed, there are few natural polysaccharides reported to activate cGAS-STING signaling for the treatment of infectious diseases. Here, we reported that Laminaran, a low molecular weight β-glucan storage polysaccharide present in brown algae, potentiates cGAS-STING signaling to promote type I IFNs production and antiviral response.
View Article and Find Full Text PDFFloralozone attenuates atherosclerotic vascular injury by regulating AMPKα/SREBP-1c pathway and down-regulating miR-33-5p.
Eur J Nutr
January 2025
College of Pharmacy, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, China.
Background: Severe disruption of lipid metabolism in vivo is one of the central mechanisms in the development of atherosclerotic vascular injury (AVI). Reverse cholesterol transport (RCT) plays a pivotal role in eliminating excess cholesterol, preventing lipid deposition in the aorta, and reducing plaque formation associated with AVI. Floralozone (FL) reduces endothelial cell injury in AVI rats by regulating sphingosine-1-phosphate (S1P) expression.
View Article and Find Full Text PDFRe-evaluation of the -Glucosyltransferase IroB Illuminates Its Ability to -Glucosylate Non-native Triscatecholate Enterobactin Mimics.
Biochemistry
January 2025
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
The pathogen-associated -glucosyltransferase IroB is involved in the biosynthesis of salmochelins, -glucosylated derivatives of enterobactin (Ent), which is a triscatecholate siderophore of enteric bacteria including and . Here, we reassess the ability of IroB to -glucosylate non-native triscatecholate mimics of Ent, which may have utility in the design and development of siderophore-based therapeutics and diagnostics. We establish TRENCAM (TC) and MECAM (MC), synthetic Ent analogs with tris(2-aminoethyl)amine- or mesitylene-derived backbones replacing the trilactone core of Ent, respectively, and their monoglucosylated congeners as substrates of IroB.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!