2. Academic Validation
  3. Piceatannol, a natural trans-stilbene compound, inhibits human glyoxalase I

Piceatannol, a natural trans-stilbene compound, inhibits human glyoxalase I

  • Bioorg Med Chem Lett. 2017 Mar 1;27(5):1169-1174. doi: 10.1016/j.bmcl.2017.01.070.
Ryoko Takasawa 1,  Haruka Akahane 2,  Hikari Tanaka 2,  Nami Shimada 2,  Takayuki Yamamoto 3,  Hiroko Uchida-Maruki 3,  Masahiko Sai 3,  Atsushi Yoshimori 4,  Sei-Ichi Tanuma 5
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Genome & Drug Research Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: takasawa@rs.noda.tus.ac.jp.
  • 2 Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • 3 Health Science Research Center, Morinaga & Co., Ltd., 2-1-1 Shimosueyoshi, Tsurumi-ku, Yokohama 230-8504, Japan.
  • 4 Institute for Theoretical Medicine, Inc., Tokyo Institute of Technology Yokohama Venture Plaza W101, 4259-3 Nagatsuda, Midori, Yokohama, Kanagawa 226-8510, Japan.
  • 5 Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Genome & Drug Research Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
PMID: 28169168 DOI: 10.1016/j.bmcl.2017.01.070
Abstract

Human glyoxalase I (GLO I), a rate-limiting Enzyme for detoxification of methylglyoxal (MG), a by-product of glycolysis, is known to be a potential therapeutic target for Cancer. Here, we searched new scaffolds from natural compounds for designing novel GLO I inhibitors and found trans-stilbene scaffold. We examined the inhibitory abilities to human GLO I of commercially available trans-stilbene compounds. Among them, piceatannol was found to have the most potent inhibitory activity against human GLO I. Piceatannol could inhibit the proliferation of human lung Cancer NCI-H522 cells, which are dependent on GLO I for survival, in a dose- and time-dependent manner. In addition, piceatannol more significantly inhibited the proliferation of NCI-H522 cells than that of NCI-H460 cells, which are less dependent on GLO I. Importantly, overexpression of GLO I in NCI-H522 cells resulted in less sensitive to the antiproliferative activity of piceatannol. Taken together, this is the first report demonstrating that piceatannol inhibits GLO I activity and the GLO I-dependent proliferation of Cancer cells. Furthermore, we determined a pharmacophore for novel inhibitors of human GLO I by computational simulation analyses of the binding mode of piceatannol to the Enzyme hot spot in the active site. We suggest that piceatannol is a possible lead compound for the development of novel GLO I inhibitory Anticancer drugs.

Keywords

Anticancer; Glyoxalase I; Inhibitor; Piceatannol; Stilbenes.

Figures