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

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

  • Bioorg Med Chem Lett. 2010 Feb 1;20(3):963-5. doi: 10.1016/j.bmcl.2009.12.055.
Satoshi Miyanaga 1,  Hiroaki Sakurai,  Ikuo Saiki,  Hiroyasu Onaka,  Yasuhiro Igarashi
Affiliations

Affiliation

  • 1 Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
PMID: 20056543 DOI: 10.1016/j.bmcl.2009.12.055
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.

Figures