title: 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.affiliation: Division of Medicinal Chemsitry and Pharmacognosy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.forename: Angela A
authors.initials: AA
authors.lastname: Salim
authors.forename: Bao-Ning
authors.initials: BN
authors.lastname: Su
authors.forename: Qiuwen
authors.initials: Q
authors.lastname: Mi
authors.forename: Hee-Byung
authors.initials: HB
authors.lastname: Chai
authors.forename: Soedarsono
authors.initials: S
authors.lastname: Riswan
authors.forename: Leonardus B S
authors.initials: LB
authors.lastname: Kardono
authors.forename: Agus
authors.initials: A
authors.lastname: Ruskandi
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D035801:Amomum / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003512:Cyclohexanones; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007941:Leukemia P388; D010946:Plants, Medicinal / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000473:Alkanes; D000972:Antineoplastic Agents, Phytogenic; D003512:Cyclohexanones; D013141:Spiro Compounds; C476177:aculeatin A; C476176:aculeatin B