Reversibility of the thia-Michael reaction of cytotoxic C5-curcuminoid and structure-activity relationship of bis-thiol-adducts thereof

Aki Kohyama, Michihiro Fukuda, Shunsuke Sugiyama, Hiroyuki Yamakoshi, Naoki Kanoh, Chikashi Ishioka, Hiroyuki Shibata, Yoshiharu Iwabuchi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

C5-curcuminoids [a.k.a. bis(arylmethylidene)acetones] are curcumin analogues bearing a reactive cross-conjugated dienone structure essential for eliciting cytotoxicity. To gain insight into the mode of action of C5-curcuminoids, we investigated the reversibility of the thia-Michael reaction of 1,5-bis(3,5-bis(methoxymethoxy)phenyl)-1,4-pentadiene-3-one, named GO-Y030 which is the most potent cytotoxic C5-curcuminoid, using spectroscopic methods. A panel of GO-Y030-bis-thiol-adducts were synthesized and the structure-reactivity relationship regarding the retro thia-Michael reaction as well as the cell growth inhibitory activity against human colon cancer HCT116 were evaluated. Some C5-curcuminoid thiol-adducts exhibited comparable cytotoxicity with GO-Y030, demonstrating their potential use as prodrugs. These results imply that C5-curcuminoids elicit cytotoxicity by covalently interacting with various biothiols via a reversible thia-Michael reaction.

Original languageEnglish
Pages (from-to)10683-10687
Number of pages5
JournalOrganic and Biomolecular Chemistry
Volume14
Issue number45
DOIs
Publication statusPublished - 2016 Jan 1

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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