Terpene conjugates of diaminedichloridoplatinum(II) complexes: antiproliferative effects in HL-60 leukemia, 518A2 melanoma, and HT-29 colon cancer cells

Chem Biodivers. 2008 Aug;5(8):1645-1659. doi: 10.1002/cbdv.200890152.

Abstract

Twenty-eight [6-(aminomethyl)nicotinate]dichloridoplatinum(II) complexes 1 esterified with various terpene alcohols either directly or via alkyl spacers were tested for antiproliferative activity in human 518A2 melanoma and HL-60 leukemia cells. Generally, conjugates with menthanes and polycyclic sesquiterpenes attached via propane-1,2-diyl spacers were most active. In the melanoma cells, the propane-1,2-diyl-spacered conjugates of (-)-menthol (1a(2')), (+)-neomenthol (1b(2')), (-)-carvomenthol (1h(2')), and (-)-isolongifolol (1n(2')) displayed growth inhibition at IC(50)<4 microM which is ten times smaller than that of cisplatin. The stationary diamino ligand was also crucial. The (-)-menthyl ester complexes with 2,3-diaminopropanoate (9a) and 2,4-diaminobutanoate (10a) ligands caused a greater and persistent growth inhibition in HT-29 colon cancer cells upon long-term exposure when compared to the 6-(aminomethyl)nicotinate analogue 1a. The cedrenyl ester 1l and the menthoxyisopropyl ester 1a(2') proved most efficacious in all three tumor cell lines. The DNA binding of complexes 1 was assessed by electrophoretic band-shift experiments and found correlated to the terpene structure but not to the observed antiproliferative activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • HT29 Cells
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Magnetic Resonance Spectroscopy / standards
  • Melanoma / pathology*
  • Molecular Conformation
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology*
  • Reference Standards
  • Stereoisomerism
  • Structure-Activity Relationship
  • Terpenes / chemistry*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Organoplatinum Compounds
  • Terpenes