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

作者：Miyanaga Satoshi; Sakurai Hiroaki; Saiki Ikuo; Onaka Hiroyasu; Igarashi Yasuhiro^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(3): 963-965.

DOI：10.1016/j.bmcl.2009.12.055

• Invasion
• Angiogenesis
• BU-4664L
• Dibenzodiazepine

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.

• 出版日期2010-2-1