title: 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.affiliation: Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyanaga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Onaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: 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
chemical_list: 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