Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610, NSC 721648)

J Med Chem. 2008 Aug 28;51(16):5135-9. doi: 10.1021/jm800418z. Epub 2008 Jul 31.

Abstract

New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, none of the new compounds approached 5 in terms of antitumor potency. For 5, binding to the aryl hydrocarbon receptor appeared to be necessary but not sufficient for growth inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / pharmacology
  • Benzothiazoles / chemical synthesis*
  • Benzothiazoles / pharmacology
  • Benzoxazoles / chemical synthesis*
  • Benzoxazoles / pharmacology
  • Breast Neoplasms / drug therapy
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Humans
  • Receptors, Aryl Hydrocarbon / metabolism
  • Structure-Activity Relationship

Substances

  • 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole
  • Antineoplastic Agents
  • Benzopyrans
  • Benzothiazoles
  • Benzoxazoles
  • Receptors, Aryl Hydrocarbon