In vitro pharmacological study of monomeric platinum(III) hematoporphyrin IX complexes

Invest New Drugs. 2011 Oct;29(5):742-51. doi: 10.1007/s10637-010-9412-8. Epub 2010 Mar 13.

Abstract

Three stable mononuclear hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) complexes of Pt(III), namely cis-[ Pt(III)(NH(3))(2)(Hp(-3H))(H(2)O)(2)].H(2)O 1, [Pt(III)(Hp(-3H))(H(2)O)(2)].H(2)O 2 and [Pt(III)((O,O)Hp(-2H))Cl(H(2)O)(3)] 3 with distorted octahedral structure and (d(z)2)(1) ground state have been tested in vitro for antineoplastic activity in a panel of tumor cell lines. The novel platinum(III) complexes showed cytotoxic activity in a concentration-dependent manner with IC(50) values comparable to those of referent cytotoxic agent cisplatin together with lower cytotoxicity against renal cells. Further detailed evaluation of the active analogue 2 and the less active complex 3 showed that their potency greatly correlates with the ability to induce apoptosis and to bind DNA. Despite the structural dissimilarities between complex 2 and cisplatin, their DNA-adducts were equally effectively recognized and repaired by the nucleotide excision repair system. Complex 2 showed quite superior ability to accumulate in K-562 cells relative to cisplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Cell Line, Tumor
  • DNA Fragmentation / drug effects
  • DNA Repair / drug effects
  • DNA, Neoplasm / metabolism
  • Drug Screening Assays, Antitumor
  • Electron Spin Resonance Spectroscopy
  • HEK293 Cells
  • Hematoporphyrins / chemistry
  • Hematoporphyrins / pharmacology*
  • Hematoporphyrins / toxicity
  • Humans
  • Kidney / drug effects
  • Kidney / pathology
  • Kinetics
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / toxicity
  • Solutions
  • Spectrophotometry, Ultraviolet

Substances

  • DNA, Neoplasm
  • Hematoporphyrins
  • Organoplatinum Compounds
  • Solutions