title: Effects of 9,10-dihydroxy-4,4-dimethyl-5,8-dihydro-1(4H)-anthracenone derivatives on tumor cell respiration.
abstract: A series of tricyclic hydroquinones, incorporating a carbonyl group in the ortho position relative to the phenol function, were tested as inhibitors of oxygen uptake against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. The title compound, which proved to be the most active one, also exhibited low micromolar dose-dependent growth inhibition of the human tumor U937 cell line (human monocytic leukemia). A tentative structure-activity relationship is proposed for these substances. A comparison between the cytotoxicities of the title compound and 4,4-dimethyl-5,8-dihydroxynaphthalene-1-one, with their activities as inhibitors of oxygen uptake by the TA3-MTX-R cell line, is presented. Also, the inhibition of oxygen uptake by 6-(4-methylpent-3-enyl)-1,4-naphthoquinone was determined and compared with its reported cytotoxicity toward P-388 (murine lymphocytic leukemia), A-549 (human lung carcinoma), HT-29 (human colon carcinoma), and MEL-28 (human melanoma) cells. The inhibition of oxygen uptake by TA3-MTX-R cells is useful as a quick test for preliminary screening of possible anticancer activity.
authors.affiliation: Department of Organic and Physical Chemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago. raraya@ciq.uchile.cl
authors.forename: Ramiro
authors.initials: R
authors.lastname: Araya-Maturana
authors.forename: Wilson
authors.initials: W
authors.lastname: Cardona
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Cassels
authors.forename: Tomás
authors.initials: T
authors.lastname: Delgado-Castro
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
authors.forename: Dante
authors.initials: D
authors.lastname: Miranda
authors.forename: Mario
authors.initials: M
authors.lastname: Pavani
authors.forename: Hernán
authors.initials: H
authors.lastname: Pessoa-Mahana
authors.forename: Jorge
authors.initials: J
authors.lastname: Soto-Delgado
authors.forename: Boris
authors.initials: B
authors.lastname: Weiss-López
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D051379:Mice; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C512538:4,4-dimethyl-5,8-dihydroxynaphthalene-1-one; D000873:Anthracenes; D000970:Antineoplastic Agents; D009281:Naphthalenes