F-36316 A and B, novel vasoactive compounds, isolated from Incrucipulum sp. SANK 10414
Yuki Hirota-Takahata1, Yoko Ishimoto2, Emi Kurosawa1
1Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd, Tokyo, Japan.
The Journal of Antibiotics
|August 10, 2017
Summary
Researchers discovered novel compounds F-36316 A and B from Incrucipulum sp. These compounds, new 3-acylated tetronic acid homologs, altered endothelial cell morphology and suppressed vascular endothelial growth factor (VEGF)-induced vascular permeability.
Area of Science:
- Natural Product Chemistry
- Pharmacology
- Cell Biology
Background:
- Vasoactive compounds are crucial for regulating vascular function.
- Screening programs are essential for identifying novel bioactive molecules.
- Endothelial and fibroblast co-culture assays provide a model for studying vascular effects.
Purpose of the Study:
- To isolate and characterize novel vasoactive compounds from Incrucipulum sp.
- To investigate the effects of isolated compounds on endothelial cell morphology.
- To evaluate the compounds' impact on vascular endothelial growth factor (VEGF)-induced vascular permeability.
Main Methods:
- Isolation of compounds from cultured broth of Incrucipulum sp. SANK 10414.
- Structure elucidation using physicochemical data and spectral analyses.
- In vitro co-culture assay with endothelial and fibroblast cells.
- In vivo study on VEGF-induced vascular permeability in mice.
Main Results:
- Two new 3-acylated tetronic acid homologs, F-36316 A and B, were isolated.
- F-36316 A and B induced distinct endothelial cell morphological changes with EC50 values of 1.8 and 11.7 μM, respectively.
- Both F-36316 A and B suppressed VEGF-induced vascular permeability in mice.
Conclusions:
- Incrucipulum sp. produces novel 3-acylated tetronic acid homologs with significant bioactivity.
- F-36316 A and B exhibit potent endothelial cell modulating effects and anti-angiogenic properties.
- These compounds represent potential leads for developing new therapeutic agents targeting vascular diseases.
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