30-, 31-, and 32-hydroxybullatacinones: bioactive terminally hydroxylated annonaceous acetogenins from Annona bullata.
From Annona bullata, three more pairs of new ketolactone Annonaceous acetogenins were isolated by bioactivity-directed isolation. They are hydroxylated adjacent bistetrahydrofuran (THF) acetogenins and are named (2,4-cis and trans)-32-hydroxybullatacinone (1 and 2), (2,4-cis and trans)-31-hydroxybullatacinone (3 and 4), and (2,4-cis and trans)-30-hydroxybullatacinone (5 and 6). The structures were elucidated by analysis of the 1H- and 13C-nmr spectra of 1-6 and their acetates and the ms of their tri-trimethylsilyl (TMSi) derivatives as compared with bullatacinone [7]. This is the first time that Annonaceous acetogenins with OH groups at successive positions near the end of the aliphatic chain have been reported. All of the new compounds showed potent activities in the brine shrimp lethality test and against human solid tumor cells in culture, with selectivities exhibited especially toward the colon cancer cell line (HT-29).
Gu
Z M
ZM
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Fang
X P
XP
Miesbauer
L R
LR
Smith
D L
DL
McLaughlin
J L
JL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D001156:Artemia; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010946:Plants, Medicinal / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D004317:Doxorubicin