Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Four tunicamycin class compounds, tunicamycin VII (), tunicamycin VIII (), corynetoxin U17a (), and tunicamycin IX (), were isolated from the culture broth of the marine-derived actinomycete sp. MBTG32. The strain was identified using the 16S rDNA sequencing technique, and the isolated strain was closely related to . The structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported NMR data. Compounds - showed potent antibacterial activities against Gram-positive bacteria, especially with MIC values of 0.13-0.25 µg/mL. Through a recombinant enzyme assay and overexpression analysis, we found that the isolated compounds exerted potent inhibitory effects on MurNAc-pentapeptide translocase (MraY), with IC values of 0.08-0.21 µg/mL. The present results support that the underlying mechanism of action of tunicamycins isolated from marine-derived sp. is also associated with the inhibition of MraY enzyme activity in .
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11277991 | PMC |
| http://dx.doi.org/10.3390/md22070293 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tunicamycins from Marine-Derived Inhibit MurNAc-Pentapeptide Translocase in .
Mar Drugs
June 2024
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea.
Article Synopsis
- Four tunicamycin compounds were identified from a marine actinomycete strain, revealing their potential as antibacterial agents.
- The compounds demonstrated strong activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values between 0.13-0.25 µg/mL.
- They were found to inhibit the MraY enzyme, crucial for bacterial cell wall synthesis, with inhibitory concentrations (IC) ranging from 0.08-0.21 µg/mL.
[Bridge between Total Synthesis of Bioactive Natural Products and Development of Drug Leads].
Yakugaku Zasshi
April 2022
Faculty of Pharmaceutical Sciences, Hokkaido University.
Although natural products are rich sources for drug discovery, only a small percentage of natural products themselves have been approved for clinical use, thus it is necessary to modulate various properties, such as efficacy, toxicity, and metabolic stability. A question in natural product drug discovery is how to logically design natural product derivatives with desired biological properties. This review describes our recent studies regarding the medicinal chemistry of tunicamycin.
View Article and Find Full Text PDFSynthetic Sansanmycin Analogues as Potent Translocase I Inhibitors.
J Med Chem
December 2021
School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
Herein, we report the design and synthesis of inhibitors of () phospho-MurNAc-pentapeptide translocase I (MurX), the first membrane-associated step of peptidoglycan synthesis, leveraging the privileged structure of the sansanmycin family of uridylpeptide natural products. A number of analogues bearing hydrophobic amide modifications to the pseudo-peptidic end of the natural product scaffold were generated that exhibited nanomolar inhibitory activity against MurX and potent activity against . We show that a lead analogue bearing an appended neopentylamide moiety possesses rapid antimycobacterial effects with a profile similar to the frontline tuberculosis drug isoniazid.
View Article and Find Full Text PDFSynthesis and evaluation of cyclopentane-based muraymycin analogs targeting MraY.
Eur J Med Chem
April 2021
Department of Chemistry, Duke University, Durham, NC, 27708, United States. Electronic address:
Antibiotic resistance is one of the most challenging global health issues and presents an urgent need for the development of new antibiotics. In this regard, phospho-MurNAc-pentapeptide translocase (MraY), an essential enzyme in the early stages of peptidoglycan biosynthesis, has emerged as a promising new antibiotic target. We recently reported the crystal structures of MraY in complex with representative members of naturally occurring nucleoside antibiotics, including muraymycin D2.
View Article and Find Full Text PDFIdentification of potential non-nucleoside MraY inhibitors for tuberculosis chemotherapy using structure-based virtual screening.
J Biomol Struct Dyn
July 2022
Department of BioMolecular Sciences, Division of Medicinal Chemistry, University of Mississippi, University, MS, USA.
The efforts to limit the spread of the tuberculosis epidemic have been challenged by the rise of drug-resistant strains of (), the causative agent of tuberculosis. It is critical to discover new chemical scaffolds acting on novel or unexploited targets to beat this drug-resistant pathogen. MraY (phospho-MurNAc-pentapeptide translocase or translocase I) is an validated target for antibacterials-discovery.
View Article and Find Full Text PDF