ICM0301s, new angiogenesis inhibitors from Aspergillus sp. F-1491. I. Taxonomy, fermentation, isolation and biological activities

• Published in: Journal of antibiotics Vol. 57; no. 2; p. 97
• Main Authors: Kumagai, Hiroyuki, Someno, Tetsuya, Dobashi, Kazuyuki, Isshiki, Kunio, Ishizuka, Masaaki, Ikeda, Daishiro
• Format: Journal Article
• Language: English
• Published: Japan 01-02-2004
• Subjects: Angiogenesis Inhibitors - isolation & purification; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - toxicity; Animals; Antifungal Agents - pharmacology; Antineoplastic Agents - pharmacology; Aorta - drug effects; Aorta - growth & development; Aspergillus - chemistry; Aspergillus - classification; Aspergillus - metabolism; Cell Line; Cell Line, Tumor; Chromatography, High Pressure Liquid; Epoxy Compounds - isolation & purification; Epoxy Compounds - pharmacology; Epoxy Compounds - toxicity; Fermentation; Fungi - drug effects; Humans; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Naphthalenes - isolation & purification; Naphthalenes - pharmacology; Naphthalenes - toxicity; Organ Culture Techniques; Rats; Rats, Sprague-Dawley
• ISSN: 0021-8820
• DOI: 10.7164/antibiotics.57.97

In the course of screening program for inhibitors of angiogenesis, novel substances designated as ICM0301A approximately H (1 approximately 8) were isolated from the culture broth of Aspergillus sp. F-1491. ICM0301s inhibited the growth of human umbilical vein endothelial cells (HUVECs) induced by basic fibroblast growth factor (bFGF) with IC50 values of 2.2 approximately 9.3 microg/ml. ICM0301A (1) showed significant anti-angiogenic activity at lower than 10 microg/ml in the angiogenesis model using rat aorta cultured in fibrin gel. ICM0301s showed very low cytotoxicity against various tumor cells. Furthermore, 1CM0301A did not show any toxic symptom in mice by intraperitoneal injection at 100 mg/kg.