title: Anti-austeric activity of phenolic constituents of seeds of Arctium lappa.
abstract: From seeds of Arctium lappa L. (Asteraceae) we obtained arctigenin (1), arctiin (2), chlorogenic acid (3), 4,5-dicaffeoylquinic acid (4), 3,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), matairesinol (11), isolappaol A (12), lappaol F (14), and lappaol B (15), together with 1:1 mixtures of isolappaol C (7) and lappaol C (8), arctignan E (9) and arctignan D (10), and 12 and lappaol A (13), while 3,3',4'-tri-O-demethylarctigenin (16), 3,3'-di-O-demethyl-4'-dehydroxyarctigenin (17), and 3-O-demethylarctigenin (18) were obtained by anaerobic microbiological metabolism of 1. Then, we evaluated the in vitro preferential cytotoxic activity of these pure compounds and 1:1 mixtures, together with enterodiol (19) and enterolactone (20), against human pancreatic cancer PANC-1 cells in nutrient-deprived medium (NDM). Among them, 1 and 18 showed potent activity, with PC50 values of 1.75 and 4.38 microM, respectively, while 11, 15, and 17 showed mild activity with PC50 values of 31.1, 30.9, and 38.7 microM, respectively. By comparing their structures and PC50 values, the following structural moieties could be concluded to be important for the preferential cytotoxicity of 1: 1) the 3-hydroxy-4-methoxyphenyl group at the 2-position on the gamma-butyrolactone ring, 2) the less polar substituent at the 3-position on the gamma-butyrolactone ring, and 3) the gamma-butyrolactone ring.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. tezuka@inm.u-toyama.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tezuka
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Suresh
authors.initials: S
authors.lastname: Awale
authors.forename: Feng
authors.initials: F
authors.lastname: Lia
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yomoda
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kadota
mesh_terms: D031170:Arctium / Q000737:chemistry*; D001421:Bacteria, Anaerobic / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D010636:Phenols