Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1)

J Med Chem. 2006 Dec 28;49(26):7897-901. doi: 10.1021/jm061077m.

Abstract

The design and synthesis of antitumor imidazothiazole guanylhydrazones are reported. The compounds were submitted to NCI for testing. All but one were more active than methyl-GAG. A few compounds were selected for further studies in search of a possible mechanism of action. The results from these studies and a final search with the NCI COMPARE algorithm suggest that the guanylhydrazones described in this paper are acting through a novel mechanism of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosylmethionine Decarboxylase / metabolism
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Drug Screening Assays, Antitumor
  • HL-60 Cells / drug effects
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Molecular Structure
  • Neoplasms / drug therapy
  • Structure-Activity Relationship
  • Thiazoles / chemistry*
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Hydrazones
  • Thiazoles
  • Adenosylmethionine Decarboxylase