title: 9-hydroxyellipticine and derivatives as chemotherapy agents.
abstract: The hydroxy group in 9-hydroxyellipticines increases the apparent affinity for DNA, stabilisation of toposiomerase II-DNA cleavable complex, oxidation to reactive quinone-imine intermediates, phosphorylation of p53 suppressor proteins and cytotoxicity relative to the parent ellipticines. Recent studies have focused on the mechanism of inhibition of phosphorylation of the mutant type of p53 protein, structural characterisation of the drug-DNA complex, the synthesis of carbohydrate derivatives and calculations of physical parameters, including dipole moments, as potential screens to allow identification of new active derivatives. Derivatisation at the 2- and 9-positions has lead to significant improvements in the in vivo activity of the 9-hydroxyellipticine derivatives and has provided important insights into the mechanism of action of these compounds.
authors.affiliation: School of Chemistry, The University of Sydney, N.S.W. 2006, Australia. harding@chem.usyd.edu.au
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Harding
authors.forename: Annaleise R
authors.initials: AR
authors.lastname: Grummitt
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004611:Ellipticines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D004611:Ellipticines; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53; D004247:DNA; C008009:9-hydroxyellipticine