Antitumor activity of 4-phenyl-1-arylsulfonylimidazolidinone, DW2143

Cancer Lett. 1999 Jun 1;140(1-2):177-87. doi: 10.1016/s0304-3835(99)00070-1.

Abstract

We examined the ability of sulfonylurea derivative, DW2143 (4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl]-4,5-dihydro-2-imida zolone hydrochloride), to inhibit the growth of tumor cells in vitro and in vivo. When its anti-proliferative activities were tested on five murine tumor (B 16, Colon26, E1-4, 3LL and P388) and nine human tumor (BxPC-3, HepG2, Lovo, MCF-7, NCI-H69, SW480, WiDR, KB and KBV20C) cells of diverse tissue origins, the in vitro antitumor activities of DW2143 were comparable to those of doxorubicin against all tumor cell lines. In addition, the anti-proliferative activities of DW2143 against KBV20C, a vincristine-resistant cell line, are similar or superior to those of doxorubicin. When the in vivo antitumor activities using three murine tumor cells were tested after oral administration of DW2143, a wide range of tumor growth inhibition was observed. Tumor growth inhibition against 3LL at doses of 50 and 100 mg/kg DW2143 was 84.3% and 47.2%, respectively, which was comparable or superior to those of doxorubicin (5 mg/kg). Tumor growth inhibition of B16 at a dose of 100 mg/kg in the DW2143-treated group was 42% as compared to 54% for doxorubicin (5 mg/kg). When mice implanted with Colon26 were tested, tumor growth inhibition at a dose of 80 mg/kg DW2143 was 36% as compared with 37% for doxorubicin (5 mg/kg). Taken together, these results indicate that the novel sulfonylurea derivative, DW2143, is an attractive candidate for further development as a useful oral anticancer drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Doxorubicin / therapeutic use
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Inhibitory Concentration 50
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Specific Pathogen-Free Organisms
  • Sulfones / therapeutic use*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Sulfones
  • Doxorubicin
  • DW 2143