RK-270D and E, Oxindole Derivatives from Streptomyces sp. with Anti-Angiogenic Activity

Abstract

Materials and Methods General Experimental ProceduresThe specific rotations were measured on a JASCO P-1020 polarimeter (JASCO Corporation, Japan) that uses a 100-mm glass microcell. UV spectra were recorded on an Optizen 2120 UV spectrophotometer (Mecasys, Korea). The IR spectra were recorded on a Bruker VERTEX80V FT-IR spectrometer (Bruker, Germany). The NMR spectra were recorded on Bruker AVANCE HD 800 NMR spectrometer (Bruker, USA) at the Korea Basic Science Institute (KBSI) in Ochang, South Korea. Chemical shifts were referenced to a residual solvent signal (DMSO-d 6 δ H 2.50, δ C 39.51). High-resolution electrospray ionization mass spectrometry (HRESIMS) data were acquired A chemical investigation of a culture extract from Streptomyces sp. RK85-270 led to the isolation and characterization of two new oxindoles, RK-270D (1) and E (2). The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and Highresolution electrospray ionization mass spectrometry (HRESIMS) experiments. Compound 1 exhibited anti-angiogenic activities against human umbilical vein endothelial cells (HUVECs) without cytotoxicity. Results of Western blot analysis revealed that 1 inhibits VEGF-induced angiogenesis in the HUVECs via VEGFR2/ p38 MAPK-mediated pathway.