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

Abstract

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.

• Authors: Hai-Xia Liu, Guo-Rui Huang, Huan-Ming Zhang, Jia-Rui Wu, Zhu-Jun Yao
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 12 Pg. 3426-30 (Jun 15 2007) ISSN: 0960-894X [Print] England
• PMID: 17433671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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