title: Annulation of substituted anthracene-9,10-diones yields promising selectively antiproliferative compounds.
abstract: Anthraquinone derivatives are well-known antiproliferative compounds, and some are currently used in cancer chemotherapy. Some families of annulated anthraquinone analogs have also been examined for antiproliferative activity, but in this regard almost nothing is known of 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones). A series of 1-azabenzanthrone derivatives, their 2,3-dihydro analogs, and congruently substituted 9,10-anthracenediones were tested against normal human fibroblasts and four human cancer cell lines. Most of the heterocyclic compounds proved to be weakly to moderately antiproliferative with IC50 values extending down to 0.86 μM, and exhibited up to 30-fold selectivity between cancer and normal cells. Both 1-azabenzanthrones and 1-aza-2,3-dihydrobenzanthrones were more potent than their anthraquinone counterparts, and almost without exception, the 2,3-dihydro compounds were more potent than the fully aromatic 1-azabenzanthrones.
authors: Faculty of Basic Sciences, Metropolitan Educational Sciences University, Avenida J.P. Alessandri 774, Ñuñoa, Santiago 7760197, Chile. vicente.castro@umce.cl
authors: Vicente
authors: V
authors: Castro-Castillo
authors: Cristian
authors: C
authors: Suárez-Rozas
authors: Natalia
authors: N
authors: Castro-Loiza
authors: Cristina
authors: C
authors: Theoduloz
authors: Bruce K
authors: BK
authors: Cassels
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; C042834:9,10-anthraquinone