Monofunctional platinum complexes showing potent cytotoxicity against human liver carcinoma cell line BEL-7402

J Med Chem. 2003 Jul 31;46(16):3502-7. doi: 10.1021/jm020593j.

Abstract

Three novel Pt(II) complexes [PtL(1)'Cl] I (L(1)' = glycine-N'-8-quinolylamide), [PtL(2)'Cl] II (L(2)' = l-alanine-N'-8-quinolylamide), and [PtL(3)Cl] III [L(3) = N-(tert-butoxycarbonyl)-l-methionine-N'-8-quinolylamide] have been synthesized and characterized. The crystal structure of complexes II and III showed that the ligands are three-coordinated with only one Cl(-) as the leaving group. Complex II crystallized in the monoclinic system with space group P2(1), a = 9.502(2) A, b = 4.724(1) A, c = 14.800(3) A, while complex III crystallized in the orthorhombic system with space group P2(1)2(1)2(1), a = 5.441(1) A, b = 12.978(3) A, c = 29.438(6) A. These complexes have been tested against a wide range of tumor cell lines including BEL-7402, HCT-116, SPC-A4, MOLT-4, P388, HL-60, A-549, SGC-7901, MKN-28, and HO-8910. Complex III is highly cytotoxic against the HCT-116 (IC(50) = 0.38 microM), SPC-A4 (IC(50) = 0.43 microM), BEL-7402 (IC(50) = 0.43 microM), and MOLT-4 (IC(50) = 0.61 microM) cell lines. The cell line most sensitive to III is human liver carcinoma cell line BEL-7402, which has a response rate of 75.1% at 6.6 x 10(-7) M, nearly 6 times higher than that of cisplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Liver Neoplasms
  • Methionine / analogs & derivatives
  • Methionine / chemical synthesis*
  • Methionine / chemistry
  • Methionine / pharmacology
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • chlorotris(N-(tert-butoxycarbonyl)methionine-N'-8-quinolylamide)platinum(II)
  • Methionine