Novel mono-tetrahydrofuran ring acetogenins, from the bark of Annona squamosa, showing cytotoxic selectivities for the human pancreatic carcinoma cell line, PACA-2.
The bark of Annona squamosa yielded three new mono-tetrahydrofuran (THF) ring acetogenins, each bearing two flanking hydroxyls and a carbonyl group at the C-9 position. These compounds were isolated using the brine shrimp lethality assay as a guide for the bioactivity-directed fractionation. (2,4-cis and trans)-Mosinone A (1) is a mixture of ketolactone compounds bearing a threo/trans/threo ring relationship and s double bond two methylene units away from the flanking hydroxyl. The other two new acetogenins differ in their stereochemistries around the THF ring; mosin B (2) has a threo/trans/erythro configuration across the ring, and mosin C (3) possesses a threo/cis/threo relative stereochemistry. Also found was annoreticuin-9-one (4), a known acetogenin that bears a threo/trans/threo ring configuration and a C-9 carbonyl and is new to this species. The structures were elucidated based on spectroscopic and chemical methods. Compounds 1-4 all showed selective cytotoxic activity against the human pancreatic tumor cell line, PACA-2, with potency 10-100 times that of Adriamycin.
Hopp
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DC
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Zeng
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L
Gu
Z M
ZM
Kozlowski
J F
JF
McLaughlin
J L
JL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001156:Artemia; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D019441:Plant Epidermis / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007783:Lactones; C107769:mosin B; C107770:mosin C; C107771:mosinone A