title: Hypoxia-inducible factor-1 inhibitory benzofurans and chalcone-derived diels-alder adducts from Morus species.
abstract: Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen concentrations and vital to many aspects of cancer biology. Bioassay-guided fractionation of the chloroform-soluble extracts of Morus species using a hypoxia response element (HRE)-dependent reporter assay led to identification of six benzofurans (1-6) and two chalcone-derived Diels-Alder adducts (7, 8) from Mori Cortex Radicis and three prenylated benzofurans (9-11) and four chalcone-derived Diels-Alder adducts (12-15) from Morus bombycis. The structure of the new 2-arylbenzofuran-type compound, moracin Q (3), was elucidated by spectroscopic methods, and the absolute configuration of 2 was determined for the first time. The selected compounds (1-3, 5, 7, 9, 10, and 12) from the cell-based reporter assay were found to inhibit hypoxia-induced HIF-1alpha accumulation in a dose-dependent manner in human hepatocelluar carcinoma cell-line Hep3B cells. Furthermore, these compounds were also active against hypoxia-induced vascular endothelial growth factor (VEGF) secretion in Hep3B cells.
authors.affiliation: Center for Molecular Cancer Research, Korean Research Institute of Biosciences and Biotechnology, Daejeon, Korea.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Dat
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002599:Chalcone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D031625:Morus / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D002599:Chalcone