Back to Search
Start Over
Biosynthetically guided structure-activity relationship studies of merochlorin A, an antibiotic marine natural product
- Publication Year :
- 2017
- Publisher :
- Germany : Wiley, 2017.
-
Abstract
- The onset of new multidrug-resistant strains of bacteria demands continuous development of antibacterial agents with new chemical scaffolds and mechanisms of action. We present the first structure–activity relationship (SAR) study of 16 derivatives of a structurally novel antibiotic merochlorin A that were designed using a biosynthetic blueprint. Our lead compounds are active against several Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are relatively nontoxic to human cell lines. Furthermore, derivative 12 c {(±)-(3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione} was found to inhibit the growth of Bacillus Calmette–Guérin (BCG)-infected cells at concentrations similar to rifampicin. These results outperform the natural product, underscoring the potential of merochlorin analogues as a new class of antibiotics. Refereed/Peer-reviewed
- Subjects :
- Erythrocytes
Sesterterpenes
medicine.drug_class
Stereochemistry
natural products
Antibiotics
Molecular Conformation
Bacillus
Bacillus subtilis
Microbial Sensitivity Tests
MRSA
010402 general chemistry
medicine.disease_cause
Gram-Positive Bacteria
01 natural sciences
Biochemistry
antibiotics
Microbiology
Cell Line
chemistry.chemical_compound
Structure-Activity Relationship
Drug Discovery
medicine
Structure–activity relationship
Animals
BCG
Horses
General Pharmacology, Toxicology and Pharmaceutics
Pharmacology
Biological Products
Natural product
biology
Dose-Response Relationship, Drug
010405 organic chemistry
Organic Chemistry
structure-activity relationships
biology.organism_classification
0104 chemical sciences
3. Good health
Anti-Bacterial Agents
chemistry
Staphylococcus aureus
Molecular Medicine
Bacteria
Enterococcus faecium
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b21233e54fa5c7ac96962d4d6618c288