Synthesis and evaluation of a fluorescent ritterazine-cephalostatin hybrid

Org Lett. 2011 Oct 7;13(19):5334-7. doi: 10.1021/ol202139z. Epub 2011 Sep 14.

Abstract

The cephalostatin and ritterazine natural products comprise a potent family of bis-steroidal pyrazines that display potent single-digit nanomolar inhibition of tumor cell growth. An active fluorescent ritterazine-cephalostatin hybrid probe was developed using detailed SAR data derived through total synthetic efforts. A combination of time course and confocal imaging studies indicate that this natural product family is rapidly taken up in tumor cells and localizes subcellularly within ER and surrounding the nuclear-ER interface.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / metabolism
  • HCT116 Cells
  • Humans
  • Molecular Structure
  • Phenazines / chemical synthesis*
  • Phenazines / metabolism
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / metabolism
  • Steroids / chemical synthesis*
  • Steroids / metabolism
  • Structure-Activity Relationship

Substances

  • Fluorescent Dyes
  • Phenazines
  • Spiro Compounds
  • Steroids