The discovery of the potent and selective antitumour agent 2-(4-amino-3-methylphenyl)benzothiazole (DF 203) and related compounds

Curr Med Chem. 2001 Feb;8(2):203-10. doi: 10.2174/0929867013373714.

Abstract

The development of a series of potent and selective antitumour agents, the 2-(4-aminophenyl)benzothiazoles, is described. The original lead compound in this series, CJM 126, exhibits nanomolar in vitro activity against certain human breast cancer cell lines. Structure-activity relationship studies within this simple antitumour benzothiazole pharmacophore revealed that 2-(4-aminophenyl) benzothiazoles bearing a 3'- methyl, 3'-bromo, 3'-iodo or 3'-chloro substituent are especially potent, extending the spectrum of in vitro antitumour activity to ovarian, lung, renal and colon carcinoma cell lines with a remarkable selectivity profile (NCI analysis). Other interesting features of this series include the highly unusual transient biphasic dose response relationship and possible unique mechanism of action (NCI COMPARE analysis). 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203) has been selected as the lead compound in this series on the basis of superior in vivo results

Publication types

  • Review

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzothiazoles
  • Humans
  • Prodrugs
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • 2-(4-aminophenyl)benzothiazole
  • Aniline Compounds
  • Antineoplastic Agents
  • Benzothiazoles
  • NSC 674495
  • Prodrugs
  • Thiazoles