Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives.

Abstract

In the screening for antitumor leads from microbial secondary metabolites, BU-4664L (1), a naturally occurring dibenzodiazepine, was found to inhibit tumor invasion and angiogenesis in vitro. Compound 1 inhibited the gelatinase activities of MMP-2 and MMP-9 and the cellular motility. Four derivatives (2-5) were synthesized from 1 and their antitumor activities were evaluated. Compounds 3 and 4 exhibited potent anti-angiogenic effects on HUVEC, together with remarkable inhibition of cell migration at nanomolar concentrations, and showed much lower cytotoxicity.

• Authors: Satoshi Miyanaga, Hiroaki Sakurai, Ikuo Saiki, Hiroyasu Onaka, Yasuhiro Igarashi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 3 Pg. 963-5 (Feb 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20056543 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• 5,10-dihydro-4,6,8-trihydroxy-10-(3,7,11-trimethyl-2,6,10-dodecatrienyl)-11H-dibenzo(b,e)(1,4)diazepin-11-one
• Angiogenesis Inhibitors
• Antineoplastic Agents
• Dibenzazepines
• Sesquiterpenes

Topics

• Angiogenesis Inhibitors (chemistry, pharmacology)
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Cells, Cultured
• Dibenzazepines (chemistry, pharmacology)
• Humans
• Mice
• Neoplasm Invasiveness (prevention & control)
• Sesquiterpenes (chemistry, pharmacology)