2. Academic Validation
  3. Indirubin 3'-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent

Indirubin 3'-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent

  • Bioorg Med Chem Lett. 2015 Apr 1;25(7):1403-6. doi: 10.1016/j.bmcl.2015.02.053.
Yoshimi Ichimaru 1,  Hiroaki Saito 1,  Taketo Uchiyama 1,  Koichi Metori 1,  Keiichi Tabata 1,  Takashi Suzuki 1,  Shinichi Miyairi 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
  • 2 School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan. Electronic address: miyairi.shinichi@nihon-u.ac.jp.
PMID: 25765906 DOI: 10.1016/j.bmcl.2015.02.053
Abstract

Indirubin is a potent inhibitor of cell cycle-related protein kinases by binding to the ATP-binding site and thus is a promising compound for development as an antitumor drug. We prepared indirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/Ind), in which the ATP-binding site orientated part was attached by non-specific alkylating group. The IC50 value of Epox/Ind at 1.7 μM in HepG2 cells is comparable to that of cisplatin (4.0 μM). Furthermore, Epox/Ind was shown to be metabolized by a HepG2 cell lysate into indirubin 3'-(O-2,3-dihydroxypropyl)oxime (E804), the sole extractable metabolite. The lower toxicity of this metabolite may explain the lack of cytotoxicity of 1 μM Epox/Ind observed in HepG2 cells beyond an initial loss of viability in the first 24h of treatment.

Keywords

Adduct; Anticancer agent; Epoxide; Indirubin; Metabolism.

Figures