Back to Search
Start Over
Antibacterial and Cytotoxic Phenyltetracenoid Polyketides from Streptomyces morookaense .
- Source :
-
Journal of natural products [J Nat Prod] 2021 Jun 25; Vol. 84 (6), pp. 1806-1815. Date of Electronic Publication: 2021 Jun 03. - Publication Year :
- 2021
-
Abstract
- Formicapyridine-type racemates, streptovertidines A ( 1 ) and B ( 2 ), a 7,24- seco -fasamycin, streptovertidione ( 3 ), and the fasamycin-type streptovertimycins I-T ( 4 - 15 ), together with 13 known fasamycin congeners ( 16 - 28 ), were isolated from soil-derived Streptomyces morookaense SC1169. Their structures were elucidated by extensive spectroscopic analysis and theoretical computations of ECD spectra. The fasamycin-type compounds 5 , 8 - 12 , 14 , and 15 exhibited activity against the drug-resistant bacteria MRSA and VRE (MIC: 1.25-10.0 μg/mL). All isolates, except 3 , 4 , 10 , and 24 , displayed cytotoxicity against at least one of the human carcinoma A549, HeLa, HepG2, and MCF-7 cells (IC <subscript>50</subscript> < 10.0 μM), of which some were also cytotoxic to the noncancerous Vero cells. Taken together, the activity data demonstrated that the fasamycin-type compounds were more selective to the tested bacteria over the mammalian cells. Structure-activity relationship analysis suggested that chlorination at C-2 in antibacterial fasamycin-type compounds improves the activity and selectivity to the bacteria. Theoretical simulations of reaction paths and chemical reactions for conversion of 3 to 1 were carried out and supported that the pyridine ring formation in formicapyridines proceeds nonenzymatically via 1,5-dicarbonyl condensation with ammonia.
- Subjects :
- Animals
Anti-Bacterial Agents isolation & purification
Antineoplastic Agents isolation & purification
Cell Line, Tumor
China
Chlorocebus aethiops
Humans
Molecular Structure
Polyketides chemistry
Polyketides isolation & purification
Soil Microbiology
Structure-Activity Relationship
Vero Cells
Anti-Bacterial Agents pharmacology
Antineoplastic Agents pharmacology
Polyketides pharmacology
Streptomyces chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6025
- Volume :
- 84
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of natural products
- Publication Type :
- Academic Journal
- Accession number :
- 34081476
- Full Text :
- https://doi.org/10.1021/acs.jnatprod.1c00208