Novel bis(carboxylato)dichlorido(ethane-1,2-diamine)platinum(IV) complexes with exceptionally high cytotoxicity

J Inorg Biochem. 2008 Dec;102(12):2072-7. doi: 10.1016/j.jinorgbio.2008.07.006. Epub 2008 Jul 23.

Abstract

(OC-6-33)-Dichlorido(ethane-1,2-diamine)dihydroxidoplatinum(IV) (1) was carboxylated using succinic- or 3-methylglutaric anhydride. The resulting bis(carboxylato)platinum(IV) complexes display free, uncoordinated carboxylic acid groups which were further derivatized with primary aliphatic alcohols. The complexes were characterized in detail by elemental analysis, ESI-MS, FT-IR, as well as multinuclear (1H, 13C, 15N, 195Pt) NMR spectroscopy. Cytotoxic properties were evaluated in four human tumor cell lines originating from ovarian carcinoma (CH1, SK-OV-3), cervical carcinoma (HeLa) and colon carcinoma (SW480) by means of the MTT assay (MTT = 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide). Structure-activity relationships showed that the cytotoxicity increased with increasing lipophilicity of the alcoholate moiety yielding IC50 values in the low micromolar or even low nanomolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Neoplasms / metabolism*
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds