Structural requirements of dictyopyrones isolated from Dictyostelium spp. in the regulation of Dictyostelium development and in anti-leukemic activity

Bioorg Med Chem. 2004 Jun 15;12(12):3203-14. doi: 10.1016/j.bmc.2004.04.001.

Abstract

Cellular slime molds are fascinating to the field of developmental biology, and have long been used as excellent model organisms for the study of various aspects of multicellular development. We have recently isolated alpha-pyronoids, named dictyopyrones A-D (1-4), from various species of Dictyostelium cellular slime molds, and it was shown that compound 3 may regulate Dictyostelium development. In this study, we synthesized dictyopyrones A-D (1-4) and their analogues, investigated the physiological role of the molecules in cell growth and morphogenesis in D. discoideum, and further verified their effects on human leukemia K562 cells. Nitrogen-containing compounds 22 and 37 strongly inhibited cell growth in K562 leukemia cells, indicating that these compounds may be utilized as novel lead compounds for anti-leukemic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Dictyostelium / chemistry*
  • Dictyostelium / cytology
  • Dictyostelium / drug effects*
  • Dictyostelium / growth & development
  • Humans
  • K562 Cells
  • Leukemia / pathology*
  • Molecular Structure
  • Pyrones / chemical synthesis
  • Pyrones / chemistry*
  • Pyrones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Pyrones