title: Mono-THF ring annonaceous acetogenins from Annona squamosa.
abstract: Continuing work on the bark of Annona squamosa Rich. (Annonaceae), directed by the brine shrimp lethality test (BST), has resulted in the isolation of three new Annonaceous acetogenins, 4-deoxyannoreticuin, cis-4-deoxyannoreticuin, and (2,4-cis and trans)-squamoxinone. The first two are additional examples of acetogenins isolated from this plant species which contain the unusual feature of an oxygen functionality at the C-9 position. They have a hydroxylated mono-THF ring with respective threo/trans/threo and threo/cis/threo relative stereochemistries. The latter compound is a ketolactone mixture which has the same relative stereochemistry around the THF ring and the same spatial relationship between the THF ring and the hydroxyl group along the aliphatic chain as 4-deoxyannoreticuin, but is two methylene units longer. Additionally, the isolated hydroxyl group is at C-11, while the THF ring starts at C-17, instead of at C-9 and C-15, respectively, as for the first two compounds. All three compounds showed moderate, but significant, cytotoxicities against a panel of six human tumor cell lines with (2,4 cis and trans)-squamoxinone showing promising selectivity against the pancreatic cell line (PACA-2).
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Hopp
authors.forename: F Q
authors.initials: FQ
authors.lastname: Alali
authors.forename: Z M
authors.initials: ZM
authors.lastname: Gu
authors.forename: J L
authors.initials: JL
authors.lastname: McLaughlin
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts / Q000302:isolation & purification* / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D010936:Plant Extracts; D015107:4-Butyrolactone