Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes

Chembiochem. 2019 Sep 2;20(17):2255-2261. doi: 10.1002/cbic.201900227. Epub 2019 Jul 19.

Abstract

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range. Insights into the structure-activity relationships are given, along with determination of the thioredoxin reductase inhibition potential, two-photon imaging of the fluorescent derivatives, and evaluation of gold uptake.

Keywords: cancer; cytotoxicity; gold; imaging agents; ligand effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology
  • Drug Screening Assays, Antitumor
  • Gold / pharmacokinetics*
  • Humans
  • Optical Imaging
  • Phosphines*
  • Structure-Activity Relationship
  • Thiocarbamates / chemical synthesis
  • Thiocarbamates / pharmacology*
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Phosphines
  • Thiocarbamates
  • Gold
  • Thioredoxin-Disulfide Reductase
  • phosphine