Venezenin: a new bioactive Annonaceous acetogenin from the bark of Xylopia aromatica.
Asimicin and a new cytotoxic Annonaceous acetogenin, venezenin [1], were isolated from the bark of Xylopia aromatica by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings and possessing a double bond located two methylenes away from a vicinal diol in the hydrocarbon chain. The structure of 1 was elucidated by 1H- and 13C-nmr, COSY, single-relayed COSY, and by HMBC techniques, and derivatization. Annomontacin 10-one [6] and 18/21-cis-annomontacin-10-one [7], two semi-synthetic mono-THF acetogenins were prepared from 1. These acetogenins showed cytotoxicity, comparable or superior to adriamycin, against three human solid tumor cell lines. Reduction of the 10-keto of 1 to the racemic OH-10 derivative enhanced the bioactivity, as did the conversion of 1 to 6 and 7. Venezenin [1], like other Annonaceous acetogenins, showed inhibition of oxygen uptake by rat liver mitochondria and demonstrated that the THF ring may not be essential to this mode of action.
Colman-Saizarbitoria
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Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacacol Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Gu
Z M
ZM
Zhao
G X
GX
Zeng
L
L
Kozlowski
J F
JF
McLaughlin
J L
JL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D001156:Artemia; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D014687:Venezuela
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; C094784:venezenin; D004317:Doxorubicin