The emergence and spread of multidrug-resistant (MDR) Gram negative bacteria presents a serious threat for public health. Novel antimicrobials that could overcome the resistance problems are urgently needed. UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a cytosolic zinc-based deacetylase that catalyzes the first committed step in the biosynthesis of lipid A, which is essential for the survival of Gram-negative bacteria. Our efforts toward the discovery of novel LpxC inhibitors are presented herein.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2017.03.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluation of a potent LpxC inhibitor for post-exposure prophylaxis treatment of antibiotic-resistant in a murine infection model.
Antimicrob Agents Chemother
December 2024
Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
LPC-233 (a.k.a.
View Article and Find Full Text PDFDesign, synthesis and evaluation of novel LpxC inhibitors containing a hydrazone moiety as Gram-negative antibacterial agents.
Eur J Med Chem
December 2024
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning, 110016, China. Electronic address:
LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To enable the development of novel LpxC inhibitors with potent antibacterial activities, several series of compounds were designed and synthesized and their antibacterial activities were evaluated against E. coli ATCC25922, P.
View Article and Find Full Text PDFDevelopment of Fragment-Based Inhibitors of the Bacterial Deacetylase LpxC with Low Nanomolar Activity.
J Med Chem
October 2024
Institute of Organic Chemistry, Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.
In a fragment-based approach using NMR spectroscopy, benzyloxyacetohydroxamic acid-derived inhibitors of the bacterial deacetylase LpxC bearing a substituent to target the uridine diphosphate-binding site of the enzyme were developed. By appending privileged fragments via a suitable linker, potent LpxC inhibitors with promising antibacterial activities could be obtained, like the one-digit nanomolar LpxC inhibitor ()- [ (LpxC C63A) = 9.5 nM; (LpxC): 5.
View Article and Find Full Text PDFModulating the biosynthesis and TLR4-interaction of lipopolysaccharide as an approach to counter gut dysbiosis and Parkinson's disease: Role of phyto-compounds.
Neurochem Int
September 2024
Department of Life Science & Bioinformatics, Assam University, Silchar, 788011, Assam, India. Electronic address:
Article Synopsis
- Parkinson's disease (PD) is a major neurodegenerative disorder and recent studies link its pathogenesis to imbalances in gut microbiota, particularly involving Gram-negative bacteria and their endotoxin, lipopolysaccharide (LPS), which triggers inflammatory responses in the gut and brain.
- Recent findings suggest there is a connection between LPS, alpha-synuclein, and toll-like receptor 4 (TLR4), indicating a mechanism that might exacerbate inflammation and neurodegeneration in PD, warranting further research.
- The review highlights the potential of plant-derived compounds as safer alternatives to current treatments, mentioning their ability to inhibit LpxC and TLR4, with promising results seen from compounds like curcumin and juglan
Discovery of Bacterial Key Genes from 16S rRNA-Seq Profiles That Are Associated with the Complications of SARS-CoV-2 Infections and Provide Therapeutic Indications.
Pharmaceuticals (Basel)
March 2024
Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi 6205, Bangladesh.
SARS-CoV-2 infections, commonly referred to as COVID-19, remain a critical risk to both human life and global economies. Particularly, COVID-19 patients with weak immunity may suffer from different complications due to the bacterial co-infections/super-infections/secondary infections. Therefore, different variants of alternative antibacterial therapeutic agents are required to inhibit those infection-causing drug-resistant pathogenic bacteria.
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!