title: Molecular modelling and cytotoxicity of substituted anthraquinones as inhibitors of human telomerase.
abstract: Molecular modelling has been carried out for a number of amine-functionalised anthraquinone derivatives to determine their extent of binding to G-tetraplex DNA and their ability to inhibit the enzymes telomerase and Taq polymerase. The results are compared to data obtained from a modified TRAP assay and show good correlation between the two methods. The findings suggest that anthraquinone derivatives of this type inhibit telomerase by stabilisation of four-stranded tetraplex structures associated with guanine-rich telomeric DNA regions.
authors.affiliation: Institute of Pharmacy and Chemistry, University of Sunderland, Sunderland SR1 3SD, UK. donald.cairns@sunderland.ac.uk
authors.forename: Donald
authors.initials: D
authors.lastname: Cairns
authors.forename: Evangelia
authors.initials: E
authors.lastname: Michalitsi
authors.forename: Terence C
authors.initials: TC
authors.lastname: Jenkins
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mackay
mesh_terms: D000880:Anthraquinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D020080:Tandem Repeat Sequences; D019914:Taq Polymerase / Q000037:antagonists & inhibitors; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D004791:Enzyme Inhibitors; D006147:Guanine; D004247:DNA; D019914:Taq Polymerase; D019098:Telomerase