Various methods for separating eleven different types of topoisomerase II (TOPO-2) inhibitors, including epipodophyllotoxins, anthracyclines, anthracenediones, anthrapyrazoles, anthracenebishydrazones, indole derivatives, aminoacridines, benzisoquinolinediones, isoflavones, bisdioxopiperazines and thiobarbituric acids, are summarized. Proper sample preparation and storage is critical to the successful analysis of some TOPO-2 inhibitors due to difficulties associated with adsorption, instability and complex biological components. Solid-phase and liquid-liquid extractions are widely used to separate TOPO-2 inhibitors from biological samples, although simple deproteinization followed by direct analysis of the supernatant is preferable to extraction based on its speed and simplicity. High-performance liquid chromatography (HPLC) is the favored method for the bioanalysis of TOPO-2 inhibitors. UV or diode array detection is generally employed for early pharmacokinetic studies, while fluorescence or electrochemical detection is used more frequently for analytes with fluorescent or oxidative-reductive properties. For analyses requiring highly sensitive and/or specific detection, electrospray mass spectrometry (ESI-MS or ESI-MS-MS) provides a suitable alternative. A comprehensive compilation of the HPLC techniques currently used to separate TOPO-2 inhibitors will aid the future development of analytical methods for new TOPO-2 inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0378-4347(01)00314-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of a novel 10-hydroxyevodiamine prodrug as a potent topoisomerase inhibitor with improved aqueous solubility for treatment of hepatocellular carcinoma.
Eur J Med Chem
December 2024
The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address:
Natural product evodiamine (Evo) and its synthetic derivatives represent an attractive dual Topo 1/2 inhibitors with broad-spectrum antitumor efficacy. However, the clinical applications of these compounds have been impeded by their poor aqueous solubility. Herein, a series of water-soluble 10-substituted-N(14)-phenylevodiamine derivatives were designed and synthesized.
View Article and Find Full Text PDFArtemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage and .
Front Pharmacol
October 2017
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
DNA topoisomerases 1 and 2 are enzymes that maintain DNA topology and play important essential genome functions, including DNA replication and transcription. Aberrant topoisomerases cause genome instability and a wide range of diseases, cancer in particular. Both Topo 1 and 2 are the targets of valuable anticancer drugs, such as camptothecin.
View Article and Find Full Text PDFLRIG1 dictates the chemo-sensitivity of temozolomide (TMZ) in U251 glioblastoma cells via down-regulation of EGFR/topoisomerase-2/Bcl-2.
Biochem Biophys Res Commun
August 2013
Department of Neurosurgery, Sir Run Run Shaw Hospital, College of Medical Sciences, Zhejiang University, Hangzhou, China.
In the current study, we aimed to understand the potential role of leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) in TMZ-resistance of U251 glioma cells. We established TMZ-resistant U251 clones (U251/TMZ cells), which expressed low level of LRIG1, but high levels of epidermal growth factor receptor (EGFR), topoisomerase-2 (Topo-2) and Bcl-2. Depletion of LRIG1 by the targeted RNA interference (RNAi) upregulated EGFR/Topo-2/Bcl-2 in U251 cells, and the cells were resistant to TMZ.
View Article and Find Full Text PDFDetection of HER2 and Topo 2 in breast cancers: comparison between MLPA and FISH approaches.
J Clin Pathol
February 2012
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy.
A significant proportion of breast cancers with HER2 amplification show simultaneous amplification or deletion of Topo 2. Amplification of Topo 2 may lead to the overexpression of the Topo 2 protein and ultimately to hypersensitivity to Topo 2 inhibitors. HER2 and Topo 2 gene status in breast cancer patients has been determined in several studies using immunohistochemistry, florescence in situ hybridisation (FISH) and multiplex ligation-dependent probe amplification (MLPA).
View Article and Find Full Text PDFStudying vertebrate topoisomerase 2 function using a conditional knockdown system in DT40 cells.
Nucleic Acids Res
August 2009
Department of Genetics, University of Cambridge, Downing St, Cambridge CB2 3EH, UK.
DT40 is a B-cell lymphoma-derived avian cell line widely used to study cell autonomous gene function because of the high rates with which DNA constructs are homologously recombined into its genome. Here, we demonstrate that the power of the DT40 system can be extended yet further through the use of RNA interference as an alternative to gene targeting. We have generated and characterized stable DT40 transfectants in which both topo 2 genes have been in situ tagged using gene targeting, and from which the mRNA of both topoisomerase 2 isoforms can be conditionally depleted through the tetracycline-induced expression of short hairpin RNAs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!