title: Natural and non-natural prenylated chalcones: synthesis, cytotoxicity and anti-oxidative activity.
abstract: A general strategy for the synthesis of 3'-prenylated chalcones was established and a series of prenylated hydroxychalcones, including the hop (Humulus lupulus L.) secondary metabolites xanthohumol (1), desmethylxanthohumol (2), xanthogalenol (3), and 4-methylxanthohumol (4) were synthesized. The influence of the A-ring hydroxylation pattern on the cytotoxic activity of the prenylated chalcones was investigated in a HeLa cell line and revealed that non-natural prenylated chalcones, like 2',3,4',5-tetrahydroxy-6'-methoxy-3'-prenylchalcone (9, IC(50) 3.2+/-0.4microM) as well as the phase 1 metabolite of xanthohumol (1), 3-hydroxyxanthohumol (8, IC(50) 2.5+/-0.5microM), were more active in comparison to 1 (IC(50) 9.4+/-1.4microM). A comparison of the cytotoxic activity of xanthohumol (1) and 3-hydroxyxanthohumol (8) with the non-prenylated analogs helichrysetin (12, IC(50) 5.2+/-0.8) and 3-hydroxyhelichrysetin (13, IC(50) 14.8+/-2.1) showed that the prenyl side chain at C-3' has an influence on the cytotoxicity against HeLa cells only for the dihydroxylated derivative. This offers interesting synthetic possibilities for the development of more potent compounds. The ORAC activity of the synthesized compounds was also investigated and revealed the highest activity for compounds 12, 4'-methylxanthohumol (4), and desmethylxanthohumol (2), with 4.4+/-0.6, 3.8+/-0.4, and 3.8+/-0.5 Trolox equivalents, respectively.
authors.affiliation: Institute of Pharmacy, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Vogel
authors.forename: Susanne
authors.initials: S
authors.lastname: Ohmayer
authors.forename: Gabi
authors.initials: G
authors.lastname: Brunner
authors.forename: Jörg
authors.initials: J
authors.lastname: Heilmann
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D001688:Biological Products / Q000737:chemistry* / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D054876:Prenylation; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001688:Biological Products; D047188:Chalcones