Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives.
Bioorganic & medicinal chemistry letters 2009 Dec 21; In press
Miyanaga S, Sakurai H, Saiki I, Onaka H, Igarashi Y
Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
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.
Keywords: BU-4664L angiogenic