title: Synthesis and cancer chemopreventive activity of zapotin, a natural product from Casimiroa edulis.
abstract: An efficient method has been developed to synthesize zapotin (5,6,2',6'-tetramethoxyflavone), a component of the edible fruit Casimiroa edulis, on a multigram scale. The synthesis utilizes a regioselective C-acylation of a dilithium dianion derived from a substituted o-hydroxyactophenone to afford a beta-diketone intermediate that can be cyclized to zapotin in good overall yield, thus avoiding the inefficient Baker-Venkataraman rearrangement pathway. Zapotin was found to induce both cell differentiation and apoptosis with cultured human promyelocytic leukemia cells (HL-60 cells). In addition, the compound inhibits 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with human bladder carcinoma cells (T24 cells), and TPA-induced nuclear factor-kappa B (NF-kappaB) activity with human hepatocellular liver carcinoma cells (HepG2 cells). These data suggest that zapotin merits further investigation as a potential cancer chemopreventive agent.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Arup
authors.initials: A
authors.lastname: Maiti
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.forename: Tamara
authors.initials: T
authors.lastname: Kondratyuk
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Croy
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D032081:Casimiroa / Q000737:chemistry*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction; D047309:Flavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D016196:S Phase / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D047309:Flavones; D016328:NF-kappa B; C517807:zapotin; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate