title: Synthesis, anticancer activity, and iron affinity of the Actinoplanes metabolite 7,8-dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione.
abstract: The first synthesis of 7,8-dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione (1), an isofuranonaphthoquinone produced by an Actinoplanes strain is described. Lactone ring opening of 6-methylfuro[3,4-c]furan-1(3H)-one (4) with ortho-lithiated veratrole (3), oxidation of product alcohol 5, and Friedel-Crafts acylation of the resulting aroylcarboxylic acid 7 afforded the mono methyl ether 2 of the target compound. The latter was obtained by demethylation of 2 with BBr(3) in 14% overall yield. While mono ether 2 was distinctly more cytotoxic than catechol 1 against a panel of five cancer cell lines, only the latter showed a siderophore-like binding affinity for Fe(III) with a complex dissociation constant K(D) of approximately 10(-29) M(3) (pM = 25.9).
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Breyer
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger-Neidnicht
authors.forename: Sebastian
authors.initials: S
authors.lastname: Knauer
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008848:Micromonosporaceae / Q000378:metabolism*; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000032:analysis
chemical_list: C542220:7,8-dihydroxy-1-methylnaphtho(2,3-c)furan-4,9-dione; D000970:Antineoplastic Agents; D005663:Furans; D009285:Naphthoquinones; D009942:Organometallic Compounds; D007501:Iron