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: Yasufumi Wada, Yu Harayama, Daigo Kamimura, Masako Yoshida, Tomoyuki Shibata, Kousaku Fujiwara, Koji Morimoto, Hiromichi Fujioka, Yasuyuki Kita
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 9 Issue 13 Pg. 4959-76 (Jul 07 2011) ISSN: 1477-0539 [Electronic] England
• PMID: 21597627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Quinones
• Thiazepines

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Mice
• Mice, Inbred BALB C
• Molecular Structure
• Neoplasms (drug therapy)
• Quinones (chemical synthesis, pharmacology, therapeutic use)
• Structure-Activity Relationship
• Thiazepines (chemical synthesis, pharmacology, therapeutic use)
• Xenograft Model Antitumor Assays