Synthesis and Biological Activity of a Photoaffinity Etoposide Probe
| Autor: | Norman Barnabé, Billy W. Day, Kwasi S. Avor, Gaik-Lean Chee, Jack C. Yalowich, Padmakumari Thampatty, Brian B. Hasinoff |
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| Rok vydání: | 2001 |
| Předmět: |
Magnetic Resonance Spectroscopy
Photochemistry Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents CHO Cells Photoaffinity Labels Cleavage (embryo) Biochemistry Mass Spectrometry chemistry.chemical_compound Epipodophyllotoxin Cricetinae Drug Discovery medicine Animals Humans Topoisomerase II Inhibitors heterocyclic compounds Enzyme Inhibitors Molecular Biology Etoposide biology Chemistry Topoisomerase Chinese hamster ovary cell Organic Chemistry Biological activity Kinetics biology.protein Molecular Medicine Topoisomerase-II Inhibitor K562 Cells DNA medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 9:1765-1771 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(01)00102-x |
| Popis: | The epipodophyllotoxin etoposide is a potent and widely used anticancer drug that targets DNA topoisomerase II. The synthesis, photochemical, and biological testing of a photoactivatable aromatic azido analogue of etoposide also containing an iodo group is described. This azido analogue should prove useful for identifying the etoposide interaction site on topoisomerase II. Irradiation of the azido analogue and an aldehyde-containing azido precursor with UV light produced changes in their UV--visible spectra that were consistent with photoactivation. The azido analogue strongly inhibited topoisomerase II and inhibited the growth of Chinese Hamster Ovary cells. Azido analogue-induced topoisomerase II--DNA covalent complexes were significantly increased subsequent to UV irradiation of drug-treated human leukemia K562 cells as compared to etoposide-treated cells. These results suggest that the photoactivated form of etoposide is a more effective topoisomerase II poison either by interacting directly with the enzyme or with DNA subsequent to topoisomerase II-mediated strand cleavage. |
| Databáze: | OpenAIRE |
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