Potential anticancer activity of naturally occurring and semisynthetic derivatives of aculeatins A and B from Amomum aculeatum.

Abstract

Activity-guided fractionation of hexanes- and CHCl 3-soluble extracts of Amomum aculeatum leaves, collected in Indonesia, led to the isolation of three new dioxadispiroketal-type ( 3- 5) and two new oxaspiroketal-type ( 6 and 7) derivatives. Nine semisynthetic derivatives ( 1a- 1h and 2a) of the parent compounds, aculeatins A ( 1) and B ( 2), were prepared. All isolates and semisynthetic compounds were tested against a small panel of human cell lines. Of these, aculeatin A ( 1; ED 50 0.2-1.0 microM) was found to be among the most cytotoxic of the compounds tested and was further evaluated in an in vivo hollow fiber assay; it was found to be active against MCF-7 (human breast cancer) cells implanted intraperitoneally at doses of 6.25, 12.5, 25, and 50 mg/kg. However, when 1 was tested using P388 lymphocytic leukemia and human A2780 ovarian carcinoma in vivo models, it was deemed to be inactive at the doses used.

• Authors: Young-Won Chin, Angela A Salim, Bao-Ning Su, Qiuwen Mi, Hee-Byung Chai, Soedarsono Riswan, Leonardus B S Kardono, Agus Ruskandi, Norman R Farnsworth, Steven M Swanson, A Douglas Kinghorn
• Journal: Journal of natural products (J Nat Prod) Vol. 71 Issue 3 Pg. 390-5 (Mar 2008) ISSN: 0163-3864 [Print] United States
• PMID: 18260638 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Alkanes
• Antineoplastic Agents, Phytogenic
• Cyclohexanones
• Spiro Compounds
• aculeatin A
• aculeatin B

Topics

• Alkanes (chemical synthesis, chemistry, isolation & purification, pharmacology)
• Amomum (chemistry)
• Animals
• Antineoplastic Agents, Phytogenic (chemical synthesis, chemistry, isolation & purification, pharmacology)
• Cyclohexanones
• Drug Screening Assays, Antitumor
• Female
• Humans
• Leukemia P388
• Plants, Medicinal (chemistry)
• Spiro Compounds (chemical synthesis, chemistry, isolation & purification, pharmacology)