title: The synthetic and biological studies of discorhabdins and related compounds.
abstract: Various analogues of the marine alkaloids, discorhabdins, have been synthesized. The strategy contains spirocyclization with phenyliodine(III) bis(trifluoroacetate) (PIFA), oxidative fragmentation of the β-amino alcohols with the hypervalent iodine reagent C(6)F(5)I(OCOCF(3))(2), the detosylation and dehydrogenation reaction of the pyrroloiminoquinone unit in the presence of a catalytic amount of NaN(3) and the bridged ether synthesis with HBr-AcOH as the key reactions. All the synthesized compounds were evaluated by in vitro MTT assay for cytotoxic activity against the human colon cancer cell line HCT-116. Furthermore, the discorhabdin A oxa analogues were also evaluated against four kinds of tumor model cells, a human colon cancer cell line (WiDr), a human prostate cancer cell line (DU-145) and murine leukemia cell lines (P388 and L1210). For the identification of the target, discorhabdin A and the discorhabdin A oxa analogue were evaluated by an HCC panel assay. In the test, discorhabdins could have a novel mode of action with the tumor cells.
authors: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Yasufumi
authors: Y
authors: Wada
authors: Yu
authors: Y
authors: Harayama
authors: Daigo
authors: D
authors: Kamimura
authors: Masako
authors: M
authors: Yoshida
authors: Tomoyuki
authors: T
authors: Shibata
authors: Kousaku
authors: K
authors: Fujiwara
authors: Koji
authors: K
authors: Morimoto
authors: Hiromichi
authors: H
authors: Fujioka
authors: Yasuyuki
authors: Y
authors: Kita