Annonaceous acetogenin mimics bearing a terminal lactam and their cytotoxicity against cancer cells

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3426-30. doi: 10.1016/j.bmcl.2007.03.084. Epub 2007 Mar 30.


Annonaceous acetogenins are a large class of naturally occurring polyketides exhibiting potent anticancer activities. Based on our previous discovery of AA005, a multi-ether mimic of natural acetogenins having potent antitumor activities and significant selectivity between normal cells and cancer cells, a new series of mimics containing a terminal lactam were designed, synthesized and evaluated. Bioactivity study against cancer cells shows that the N-methylated lactam-containing compounds 3, 4, and 5 exhibit comparable potencies to that of AA005, as well as the similar selectivity to cancer cells. Hydrocarbon-length effects of N-alkyl were further explored through synthesizing derivatives 24-26, and application of this derivation protocol to the fluorescent labeling was also investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetogenins
  • Alkanes / chemistry
  • Annonaceae / chemistry*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Fatty Alcohols / chemistry*
  • Fluorescent Dyes / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Lactams / chemical synthesis
  • Lactams / pharmacology*
  • Lactones / chemistry*
  • Models, Chemical
  • Molecular Mimicry
  • Tumor Cells, Cultured / drug effects


  • AA005
  • Acetogenins
  • Alkanes
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Fatty Alcohols
  • Fluorescent Dyes
  • Lactams
  • Lactones