Hirota-Takahata Yuki, Ishimoto Yoko, Kurosawa Emi, Iwadate Yuko, Onozawa Yoshiko, Tanaka Isshin, Tanaka Masahiro, Kobayashi Hideki
Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd, Tokyo, Japan.
Frontier Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
J Antibiot (Tokyo). 2017 Oct;70(10):981-986. doi: 10.1038/ja.2017.84. Epub 2017 Aug 9.
In the course of our screening program for vasoactive compounds using co-culture assay of endothelial cells and fibroblast cells, potent activity was detected in the cultured broth of Incrucipulum sp. SANK 10414. Two active compounds, F-36316 A and B, and a non-active homolog, F-36316 C, were isolated from the broth. The structures of F-36316 A, B and C were elucidated by physicochemical data and spectral analyses, and found to be new 3-acylated tetronic acid homologs. F-36316 A and B induced morphological changes of endothelial cells different from vascular endothelial growth factor (VEGF) or vestaines in the assay with EC values of 1.8 and 11.7 μM, respectively. Furthermore, F-36316 A and B suppressed VEGF-induced vascular permeability induction in mice.
在我们使用内皮细胞和成纤维细胞共培养试验筛选血管活性化合物的过程中，在Incrucipulum sp. SANK 10414的培养液中检测到了强效活性。从该培养液中分离出了两种活性化合物F-36316 A和B以及一种非活性同系物F-36316 C。通过物理化学数据和光谱分析阐明了F-36316 A、B和C的结构，发现它们是新型的3-酰化四羟基丁酸同系物。在试验中，F-36316 A和B诱导内皮细胞发生不同于血管内皮生长因子（VEGF）或维斯他因的形态变化，其EC值分别为1.8和11.7 μM。此外，F-36316 A和B抑制了VEGF诱导的小鼠血管通透性增加。
