De novo design of thioredoxin reductase-targeted heterometallic titanocene-gold compounds of chlorambucil for mechanistic insights into renal cancer

Chem Commun (Camb). 2019 Dec 19;56(2):297-300. doi: 10.1039/c9cc07406f.

Abstract

Here we report the design and synthesis of a chlorambucil-alkynyl (CHL-CCH) ligand, mononuclear gold(i) complex K[(CHL-CC)AuCl], 1, and heteronuclear complex (CHL-CC)Au(μ2-η2-CS3)Ti(η5-Cp)2, 2 for renal cancer. Complex 2 is significantly more cytotoxic than complex 1 and cisplatin against renal cancer cells with a high selectivity index value. The mechanism of action of these complexes against renal cancer cells was studied in detail by experimental and computational methods.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Chlorambucil / analogs & derivatives*
  • Chlorambucil / chemical synthesis
  • Chlorambucil / pharmacology*
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology*
  • Density Functional Theory
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Gold / chemistry
  • Humans
  • Kidney Neoplasms / drug therapy
  • Models, Chemical
  • Molecular Docking Simulation
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
  • Titanium / chemistry

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Enzyme Inhibitors
  • Chlorambucil
  • Gold
  • Titanium
  • Thioredoxin-Disulfide Reductase