Luteolin from Flos Chrysanthemi and its derivatives: New small molecule Bcl-2 protein inhibitors

Bioorg Med Chem Lett. 2014 Oct 1;24(19):4672-4677. doi: 10.1016/j.bmcl.2014.08.034. Epub 2014 Aug 20.

Abstract

Over-expression of the Bcl-2 anti-apoptotic proteins is closely related to tumorigenesis and associated with drug resistance. Here we report that luteolin, a main substance found in Flos Chrysanthemi, directly binds to and shows inhibitory activity against the Bcl-2 protein. We studied the binding mode of luteolin and its derivatives with target proteins, their structure-activity relationship, and their effect on the human leukemia cell line HL-60. The results suggest that luteolin and its derivatives with a benzyl group introduced to the B ring, are new small molecule Bcl-2 protein inhibitors, and their anti-tumor activity is likely related to their effect on the Bcl-2 protein.

Keywords: Anti-tumor; Apoptosis; Bcl-2 protein; Flos Chrysanthemi; Luteolin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chrysanthemum / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Flowers / chemistry*
  • HL-60 Cells
  • Humans
  • Luteolin / chemistry
  • Luteolin / isolation & purification
  • Luteolin / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / isolation & purification
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Proto-Oncogene Proteins c-bcl-2
  • Small Molecule Libraries
  • Luteolin