Design, synthesis, and biological activity of a novel non-cisplatin-type platinum-acridine pharmacophore

J Med Chem. 2001 Dec 6;44(25):4492-6. doi: 10.1021/jm010293m.

Abstract

Platinum-acridine conjugates were prepared from [PtCl2(ethane-1,2-diamine)] and the novel acridinylthioureas MeHNC(S)NMeAcr (6) and MeHNC(S)NMe(CH2CH2)NHAcr (15) by replacing one chloro leaving group in the cisplatin analogue with thiourea sulfur. In HL-60 leukemia cells, IC(50) values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 microM, respectively. In the ovarian cell lines 2008 and C13, 16 was active at micromolar concentrations and showed only partial cross-resistance with clinical cisplatin. Possible structure-activity relationships are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemical synthesis*
  • Acridines / chemistry
  • Acridines / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cisplatin / pharmacology
  • Drug Design
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Humans
  • Magnetic Resonance Spectroscopy
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology
  • Structure-Activity Relationship
  • Thiourea / analogs & derivatives*
  • Thiourea / chemical synthesis*
  • Thiourea / chemistry
  • Thiourea / pharmacology
  • Tumor Cells, Cultured

Substances

  • Acridines
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Thiourea
  • Cisplatin