Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives.
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.
Miyanaga
Satoshi
S
Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Sakurai
Hiroaki
H
Saiki
Ikuo
I
Onaka
Hiroyasu
H
Igarashi
Yasuhiro
Y
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003984:Dibenzazepines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology
C502981:5,10-dihydro-4,6,8-trihydroxy-10-(3,7,11-trimethyl-2,6,10-dodecatrienyl)-11H-dibenzo(b,e)(1,4)diazepin-11-one; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003984:Dibenzazepines; D012717:Sesquiterpenes