title: Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei.
abstract: Two new (1 and 2) and four known arylnaphthalene lignan lactones (3-6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-α-L-arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase IIα activity.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Ren
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lantvit
authors.forename: Youcai
authors.initials: Y
authors.lastname: Deng
authors.forename: Ragu
authors.initials: R
authors.lastname: Kanagasabai
authors.forename: Judith C
authors.initials: JC
authors.lastname: Gallucci
authors.forename: Tran Ngoc
authors.initials: TN
authors.lastname: Ninh
authors.forename: Hee-Byung
authors.initials: HB
authors.lastname: Chai
authors.forename: Djaja D
authors.initials: DD
authors.lastname: Soejarto
authors.forename: James R
authors.initials: JR
authors.lastname: Fuchs
authors.forename: Jack C
authors.initials: JC
authors.lastname: Yalowich
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D052117:Benzodioxoles / Q000737:chemistry; D053148:Caspase 3 / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D029803:Phyllanthus / Q000737:chemistry*; D014744:Vietnam
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D052117:Benzodioxoles; D006027:Glycosides; D007783:Lactones; D017705:Lignans; D009281:Naphthalenes; C514009:phyllanthusmin C; C000591085:phyllanthusmin D; C000591086:phyllanthusmin E; D053148:Caspase 3; D004264:DNA Topoisomerases, Type I; C010130:diphyllin