Platinum complexes with 5-methyl-5(4-pyridyl)hydantoin and its 3-methyl derivatives: synthesis and cytotoxic activity - quantitative structure-activity relationships

Arch Pharm (Weinheim). 2011 Apr;344(4):209-16. doi: 10.1002/ardp.201000182. Epub 2010 Dec 22.

Abstract

3,5-Dimethyl-5-(4-pyridyl)hydantoin (L) and its platinum(II) and platinum(IV) complexes with the general formula cis-[PtL(2) X(2) ] · n H(2) O and [PtL(2) Cl(4) ], where XCl, I and n = 2-4 were synthesized. A new Pt(IV) complex with 5-methyl-5-(4-pyridyl)hydantoin (L') with the formula cis-[Pt(L')(2) Cl(2) (OH)(2) ] · 5 H(2) O was also synthesized. The novel compounds were characterized by elemental analysis, IR, (1) H-, (13) C-, (195) Pt-NMR spectra and molar conductivity. The cytotoxic effects of these complexes were examined on three human tumor cell lines by MTT-dye reduction assay. These four new Pt(II) and Pt(IV) complexes and a set of another twelve Pt(II), Pt(IV), and Pd(II) complexes previously synthesized and tested were compiled and a QSAR model was derived in order to direct the further rational synthesis.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Hydantoins / chemistry*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology
  • Pyridines / chemistry*
  • Quantitative Structure-Activity Relationship

Substances

  • 5-methyl-5(4-pyridyl)hydantoin
  • Antineoplastic Agents
  • Hydantoins
  • Ligands
  • Organoplatinum Compounds
  • Pyridines