9-hydroxyellipticine and derivatives as chemotherapy agents

Date

2003

Authors

Grummitt, Annaleise R
Harding, Margaret

Journal Title

Journal ISSN

Volume Title

Publisher

Bentham Science Publishers Ltd

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.

Description

Keywords

Keywords: 9 hydroxyellipticine; 9-hydroxyellipticine; antineoplastic antimetabolite; DNA; DNA topoisomerase (ATP hydrolysing); ellipticine derivative; enzyme inhibitor; protein p53; animal; chemistry; drug antagonism; drug effect; human; metabolism; oxidation reduc

Citation

Source

Mini-Reviews in Medicinal Chemistry

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.2174/1389557033405377
10.2174/1389557033405377

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