TY - JOUR
T1 - Reversibility of the thia-Michael reaction of cytotoxic C5-curcuminoid and structure-activity relationship of bis-thiol-adducts thereof
AU - Kohyama, Aki
AU - Fukuda, Michihiro
AU - Sugiyama, Shunsuke
AU - Yamakoshi, Hiroyuki
AU - Kanoh, Naoki
AU - Ishioka, Chikashi
AU - Shibata, Hiroyuki
AU - Iwabuchi, Yoshiharu
N1 - Funding Information:
This research is partially supported by JSPS KAKENHI Grant Numbers 22501041 and 25670051, and by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and the Japan Agency for Medical Research and development (AMED).
Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1039/c6ob01771a
DO - 10.1039/c6ob01771a
M3 - Article
C2 - 27801454
AN - SCOPUS:84997206818
SN - 1477-0520
VL - 14
SP - 10683
EP - 10687
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 45
ER -
