title: Structure-activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids.
abstract: Previously, bioassay-guided separation led us to isolate eleven novel steroidal alkaloids named cortistatins from the marine sponge Corticium simplex. These cortistatins were classified into three types based on the chemical structure of the side chain part, that is, isoquinoline, N-methyl piperidine or 3-methylpyridine units. From the structure-activity relationship study, the isoquinoline unit in the side chain was found to be crucial for the anti-angiogenic activity of cortistatins. Cortistatin A (1) showed cytostatic growth-inhibitory activity against human umbilical vein endothelial cells (HUVECs). Cortistatin A (1) also inhibited VEGF-induced migration of HUVECs and bFGF-induced tubular formation. Although cortistatin A (1) showed no effect on VEGF-induced phosphorylation of ERK1/2 and p38, which are one of the signaling pathways for migration and tubular formation, the phosphorylation of the unidentified 110kDa protein in HUVECs was inhibited by the treatment with cortistatin A.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-Oka 1-6, Suita, Osaka, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Aoki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Daiki
authors.initials: D
authors.lastname: Tanabe
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Suna
authors.forename: Katsushiro
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsujibo
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054697:Cytostatic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D054697:Cytostatic Agents; D013256:Steroids; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3