Antiviral properties and cytotoxic activity of platinum(II) complexes with 1,10-phenanthrolines and acyclovir or penciclovir

J Inorg Biochem. 2004 Aug;98(8):1385-90. doi: 10.1016/j.jinorgbio.2004.04.018.

Abstract

Platinum compounds containing an aromatic diimine (1,10-phenanthroline or 2,9-dimethyl-1,10-phenanthroline; phen and Me(2)phen, respectively) and antiviral guanosine-type ligands (acyclovir or penciclovir; acy and pen, respectively) have been synthesised. These compounds maintain the antiviral activity against Herpes Symplex Virus (HSV) and have greater efficacy than free acyclovir or penciclovir against Cytomegalovirus (CMV); in both cases the species with Me(2)phen are more active. The same complexes are effective against tumor cell proliferation which also results to be dependent upon the nature of the diimine ligand: all compounds containing Me(2)phen being more active than those containing phen. Although in vivo some complexes significantly reduce tumor cell proliferation, nevertheless, they do not appear to significantly affect the life time expectancy of the treated mice. The greater cytotoxicity of compounds with Me(2)phen may result from a higher reactivity towards cellular components, such as glutathione, which could cause release of the diimine, known to be highly cytotoxic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / analogs & derivatives*
  • Acyclovir / chemistry
  • Acyclovir / metabolism
  • Acyclovir / pharmacology
  • Animals
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / metabolism
  • Antiviral Agents* / pharmacology
  • Cell Line, Tumor / drug effects
  • Cytomegalovirus / drug effects
  • Guanine
  • Humans
  • Intercalating Agents / chemistry
  • Intercalating Agents / metabolism
  • Intercalating Agents / pharmacology
  • Mice
  • Molecular Structure
  • Phenanthrolines* / chemistry
  • Phenanthrolines* / metabolism
  • Phenanthrolines* / pharmacology
  • Platinum Compounds* / chemistry
  • Platinum Compounds* / metabolism
  • Platinum Compounds* / pharmacology
  • Simplexvirus / drug effects

Substances

  • Antiviral Agents
  • Intercalating Agents
  • Phenanthrolines
  • Platinum Compounds
  • penciclovir
  • Guanine
  • 1,10-phenanthroline
  • Acyclovir