title: Bioassay-guided isolation of constituents of Piper sarmentosum using a mitochondrial transmembrane potential assay.
abstract: Bioassay-guided fractionation was conducted on a chloroform-soluble extract of the aerial parts of Piper sarmentosum collected in Vietnam, monitored by a mitochondrial transmembrane potential assay using HT-29 human colon cancer cells. This led to the isolation of four new C-benzylated dihydroflavones, sarmentosumins A-D (1-4), as well as 14 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Among these compounds, 1-4 as well as five known C-benzylated dihydroflavones (5-9) and a piperamide, pipercallosine (11), were found to induce apoptosis in HT-29 cells by moderately reducing the mitochondrial transmembrane potential (ΔΨm), with ED50 values ranging from 1.6 to 13.6 μM. Furthermore, 7-methoxydichamanetin (8) and pinocembrin (10) exhibited proteasome inhibitory activities in a human 20S proteasome bioassay with IC50 values of 3.45±0.18 and 2.87±0.26 μM, respectively. This is the first time that C-benzylated dihydroflavones have been reported to demonstrate an apoptotic effect associated with disruption of the mitochondrial transmembrane potential.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Center for Biostatistics, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Susan
authors.initials: S
authors.lastname: Matthew
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lantvit
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Tran Ngoc
authors.initials: TN
authors.lastname: Ninh
authors.forename: Heebyung
authors.initials: H
authors.lastname: Chai
authors.forename: Esperanza J
authors.initials: EJ
authors.lastname: Carcache de Blanco
authors.forename: Djaja D
authors.initials: DD
authors.lastname: Soejarto
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects*; D031701:Piper / Q000737:chemistry*; D014744:Vietnam
chemical_list: D000970:Antineoplastic Agents; D047309:Flavones