Unsaturated genistein disaccharide glycoside as a novel agent affecting microtubules

Bioorg Med Chem Lett. 2009 Sep 1;19(17):4939-43. doi: 10.1016/j.bmcl.2009.07.089. Epub 2009 Jul 22.

Abstract

Genistein, due to its recognized chemopreventive and antitumor potential, is a molecule of interest as a lead compound in drug design. While multiple molecular targets for genistein have been identified, so far neither for this isoflavonoid nor for its natural or synthetic derivatives disruption of microtubules and mitotic spindles has been reported. Here we describe such properties of the synthetic glycosidic derivative of genistein significantly more cytotoxic than genistein, 7-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-(6-O-acetyl-hex-2-ene-alpha-D-erythro-pyranosyl)genistein, shortly named G21. We found that G21 causes significant mitotic delay, frequent appearance of multipolar spindles, and alteration of the interphase microtubule array.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Disaccharides / chemical synthesis
  • Disaccharides / chemistry*
  • Disaccharides / toxicity
  • Genistein / analogs & derivatives*
  • Genistein / chemical synthesis
  • Genistein / chemistry
  • Genistein / toxicity
  • Glycosides / chemical synthesis
  • Glycosides / chemistry*
  • Glycosides / toxicity
  • Humans
  • Microtubules / drug effects*
  • Microtubules / metabolism
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / toxicity

Substances

  • 7-O-(2,3,4,6-tetra-O-acetylgalactopyranosyl)-1-4-(6-O-acetylhex-2-enepyranosyl)genistein
  • Antineoplastic Agents
  • Disaccharides
  • Glycosides
  • Tubulin Modulators
  • Genistein