F-36316 A and B, novel vasoactive compounds, isolated from Incrucipulum sp. SANK 10414

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 EC50 values of 1.8 and 11.7 μM, respectively. Furthermore, F-36316 A and B suppressed VEGF-induced vascular permeability induction in mice.