Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin- and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985699 | PMC |
| http://dx.doi.org/10.1021/ja500053x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Small molecules that targeting p53 Y220C protein: mechanisms, structures, and clinical advances in anti-tumor therapy.
Mol Divers
January 2025
School of Sciences, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, People's Republic of China.
The p53 protein is regarded as the "Guardian of the Genome," but its mutation is tumor progression and present in more than half of malignant tumors. The pro-metastatic property of mutant p53 makes a strong argument for targeting mutant p53 with new therapeutic strategies. However, mutant p53 was considered as a challenging target for drug discovery due to the lack of small molecular binding pockets.
View Article and Find Full Text PDFPbsNRs: predict the potential binders and scaffolds for nuclear receptors.
Brief Bioinform
November 2024
Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Shanghai Institute of Infectious Disease and Biosecurity, Intelligent Medicine Institute, School of Life Sciences, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China.
Nuclear receptors (NRs) are a class of essential proteins that regulate the expression of specific genes and are associated with multiple diseases. In silico methods for prescreening potential NR binders with predictive binding ability are highly desired for NR-related drug development but are rarely reported. Here, we present the PbsNRs (Predicting binders and scaffolds for Nuclear Receptors), a user-friendly web server designed to predict the potential NR binders and scaffolds through proteochemometric modeling.
View Article and Find Full Text PDFPromotion of cellular differentiation and DNA repair potential in brain cancer cells by Shankhpushpi, (Clitoria ternatea L.) with rasayana properties in vitro.
J Ayurveda Integr Med
January 2025
Centre for Ayurvedic Biology, Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India. Electronic address:
Background: Brain ageing is accompanied by the diminution of neuronal plasticity, which is correlated with the inability to respond to loss of memory, various stress-induced stimuli, and increased risk of neurodegenerative disorders. In the recent past, plant based herbal medicines are of interest over synthetic drugs for therapeutic purposes due to lower side effects. The Indian traditional medicine Ayurveda describes several herbal remedies, such as rasayana (elixirs for rejuvenation), to treat many age-related diseases.
View Article and Find Full Text PDFIdentifying Strong Neoantigen MHC-I/II Binding Candidates for Targeted Immunotherapy with SINE.
Int J Mol Sci
December 2024
Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA.
The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary.
View Article and Find Full Text PDFHow Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.
Int J Mol Sci
December 2024
Medicines Discovery Institute, Cardiff University, Cardiff CF10 3AT, UK.
DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.
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!