Catalytic inhibition of topoisomerase IIalpha by demethylzeylasterone, a 6-oxophenolic triterpenoid from Kokoona zeylanica.
In a study to evaluate celastroloids as potential anticancer agents, demethylzeylasterone (5), a 6-oxophenolic triterpenoid from Kokoona zeylanica, was found to be an inhibitor of the enzyme topoisomerase IIalpha (IC(50) = 17.6 microM). Studies of the relationship of this inhibitor to both DNA and the enzyme resulted in 5 being classified as a "catalytic inhibitor" of topoisomerase II. Demethylzeylasterone selectively inhibits the growth of the breast cancer cell line MCF-7 (IC(50) = 12.5 microM) without inhibiting the growth of non-small cell lung cancer (NCI-H460) and CNS glioma (SF-268) cell lines. This is the first report of topoisomerase II inhibitory activity in a celastroloid.
Furbacher
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Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, University of Arizona, 250 E. Valencia Road, Tucson, AZ 85706-6800, USA.
Gunatilaka
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D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001943:Breast Neoplasms; D002289:Carcinoma, Non-Small-Cell Lung; D002384:Catalysis; D004247:DNA / Q000037:antagonists & inhibitors; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004587:Electrophoresis, Agar Gel; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005260:Female; D005910:Glioma; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms; D008739:Methyl Green; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes; C439974:demethylzeylasterone; D008739:Methyl Green; D004247:DNA; D004250:DNA Topoisomerases, Type II