Cellular pharmacology of mu-[1,2-bis(diphenylphosphino)ethane]bis[(1-thio-beta-D-gluco pyranosato-S)gold(I)]: a novel antitumor agent

Anticancer Drug Des. 1986 Nov;1(3):223-34.

Abstract

SK&F 102912 (mu-[1,2-bis(diphenylphosphino)ethane]bis[(1-thio-beta-D- glucopyranosato-S)gold(I)], [(Autg)2(dppe)]) has shown reproducible and significant activity in transplantable murine tumor models and represents a structurally unique class of antineoplastic agents. A number of in vitro studies were performed to elucidate the cellular pharmacology of this gold-containing complex. [(Autg)2(dppe)] is a potent cytotoxic agent in vitro as demonstrated by its ability to inhibit the clonogenic capacity of a variety of tumor cell lines following a brief exposure to the drug. Cell-cycle analysis using HL-60 cells showed that low concentrations (2 microM) of [(Autg)2(dppe)] induced an S-phase block and higher concentrations induced a secondary block at the G1/S boundary. [(Autg)2(dppe)] had several effects on DNA metabolism and structure including preferential inhibition in cells of DNA synthesis (relative to RNA and protein synthesis) and the production of DNA single- and double-strand breaks as measured by alkaline elution. The cytoxic mechanism of this gold complex appears to be distinct from that of the monophosphine-gold complex auranofin.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Auranofin / pharmacology
  • Cell Cycle / drug effects
  • Cell Survival / drug effects
  • Chromatin / drug effects
  • DNA / biosynthesis
  • DNA Damage
  • Organometallic Compounds / pharmacology*
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Chromatin
  • Organometallic Compounds
  • SK&F 102912
  • Auranofin
  • DNA