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Cytotoxicity and DNA binding properties of the plant alkaloid burasaine.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2003 Dec; Vol. 20 (4-5), pp. 383-91. - Publication Year :
- 2003
-
Abstract
- Burasaine is a plant alkaloid isolated from the roots of several species of the Burasaia genus endemic to Madagascar. It exhibits in vitro antiplasmodial activities but the molecular basis of this biological activity is not known. The strong structural similarity with the alkaloid berberine prompted us to postulate that burasaine could interact with DNA. To test this hypothesis, we investigated the mode of binding of burasaine to DNA and tested its cytotoxic potential toward human HL-60 leukemia cells. Its inhibitory activity toward topoisomerases I and II was also studied. Absorption and melting temperature measurements attested that burasaine forms stable complexes with DNA. The results of electric linear dichroism (ELD) spectroscopy may be interpreted either by an intercalation or by an external stacking parallel to the base pairs. The affinity of burasaine for DNA is slightly lower than that of berberine and this translates at the cellular level by a reduced cytotoxicity. Burasaine does not promote DNA cleavage by human topoisomerases I or II and this likely accounts for its very weak cytotoxic potential and its very modest effects on the cell cycle progression observed at high concentrations. The study identifies DNA as a potential bioreceptor for burasaine and contributes to a better understanding of the mechanism of action of benzoquinolizine alkaloids.
- Subjects :
- Algorithms
Antineoplastic Agents, Phytogenic metabolism
Berberine analogs & derivatives
Berberine metabolism
Cell Cycle drug effects
Cell Survival drug effects
DNA Topoisomerases metabolism
HL-60 Cells
Humans
Plasmids drug effects
Spectrophotometry, Atomic
Temperature
Antineoplastic Agents, Phytogenic pharmacology
Berberine pharmacology
DNA, Neoplasm metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0928-0987
- Volume :
- 20
- Issue :
- 4-5
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 14659482
- Full Text :
- https://doi.org/10.1016/j.ejps.2003.08.007