Antitumor activity of 4,5,6,7-tetrathiocino (1,2-b: 3,4-b') diimidazolyl-1,3,8,10-tetrasubstituted-2,9-dithiones (R4-todit)

Anticancer Res. 1998 Nov-Dec;18(6A):4429-34.

Abstract

A series of derivatives belonging to a new class of compounds (R4-todit) were highly cytotoxic to a panel of leukaemia- and solid tumour-derived cell lines (IC50 = 0.06-20 microM). The most potent compound was the butyl4 derivative (IC50 = 0.06-5.1 microM); T leukaemia and melanoma cells were the most susceptible cells to this inhibitor (IC50 0.06 microM and 0.1 microM, respectively). The effect of butyl4-todit was irreversible, and led to progressive cell death. The compound showed a comparable potency against exponentially growing and stationary phase cells, and against cell lines expressing the MDR phenotype. The cytotoxicity of butyl4-todit in human normal PBL was up to 20 fold lower than that shown against T leukaemia cells. When tested for antiangiogenic activity in vivo, 1.5 mg/Kg butyl4-todit resulted in over 70% inhibition of the angiogenesis process induced in mice by Kaposi's sarcoma cell secreted products.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Culture Media
  • Doxorubicin / toxicity
  • Drug Resistance, Multiple
  • HeLa Cells
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / toxicity*
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / toxicity*
  • KB Cells
  • Leukemia, T-Cell
  • Lymphocytes / drug effects
  • Lymphocytes / pathology
  • Male
  • Melanoma
  • Mice
  • Mice, Inbred Strains
  • Neovascularization, Pathologic / prevention & control
  • Sarcoma, Kaposi / blood supply
  • Structure-Activity Relationship
  • Thiones / chemistry
  • Thiones / toxicity*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Culture Media
  • Heterocyclic Compounds, 3-Ring
  • Imidazoles
  • Thiones
  • Doxorubicin