title: Cytotoxic and NF-κB inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues.
abstract: A new caged xanthone (1), a new prenylxanthone (2), seven known xanthones, and a known sterol glucoside were isolated from the stems of Cratoxylum cochinchinense, collected in Vietnam. Compounds 1 and 2 were determined structurally by analysis of their spectroscopic data. In addition, five new (10 and 16-19) and eight known prenylated xanthone derivatives were synthesized from the known compounds α-mangostin (3) and cochinchinone A (6). Several of these substances were found to be cytotoxic toward HT-29 human colon cancer cells, with the most potent being 3,6-di-O-acetyl-α-mangostin (8, ED50, 1.0 μM), which was tested further in an in vivo hollow fiber assay, but found to be inactive at the highest dose used (20 mg/kg; ip). Of the substances evaluated in a NF-κB p65 inhibition assay, 1,3,7-trihydroxy-2,4-diisoprenylxanthone (5) exhibited the most potent activity (IC50, 2.9 μM). In a mitochondrial transmembrane potential assay, two new compounds, 1 (IC50, 3.3 μM) and 10 (IC50, 1.4 μM), and two known compounds, 3 (α-mangostin, IC50, 0.2 μM) and 11 (3,6-di-O-methyl-α-mangostin, IC50, 0.9 μM), were active. A preliminary analogue development study showed that 3,6-diacetylation and 6-benzoylation both slightly increased the cytotoxicity of α-mangostin (3), whereas methylation reduced such activity. In contrast, neither acetylation, benzoylation, nor methylation enhanced the cytotoxicity of cochinchinone A (6).
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: Susan
authors.initials: S
authors.lastname: Matthew
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lantvit
authors.forename: Tran Ngoc
authors.initials: TN
authors.lastname: Ninh
authors.forename: Heebyung
authors.initials: H
authors.lastname: Chai
authors.forename: James R
authors.initials: JR
authors.lastname: Fuchs
authors.forename: Djaja D
authors.initials: DD
authors.lastname: Soejarto
authors.forename: Esperanza J Carcache
authors.initials: EJ
authors.lastname: de Blanco
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D028084:Clusiaceae / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018547:Plant Stems / Q000737:chemistry; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D044004:Xanthones