Toward establishing structure–activity relationships for oxygenated coumarins as differentiation inducers of promonocytic leukemic cells
The present work evaluates a series of natural and synthesized oxygenated coumarins to induce differentiation in a leukemic cell line, providing insight into the correlation between structural properties of these coumarins and their in vitro leukemic differentiation activity. The presumption that so...
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Veröffentlicht in: | Bioorganic & medicinal chemistry 2009-09, Vol.17 (18), p.6547-6559 |
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Sprache: | eng |
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Zusammenfassung: | The present work evaluates a series of natural and synthesized oxygenated coumarins to induce differentiation in a leukemic cell line, providing insight into the correlation between structural properties of these coumarins and their in vitro leukemic differentiation activity.
The presumption that some coumarins might be lead compounds in the search for new differentiation agents against leukemia is based on the fact that natural coumarins, 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin (
C-
2) and 5-methoxy-6,7-methylenedioxycoumarin (
C-
1) inhibit proliferation and induce differentiation in U-937 cells [Riveiro, M. E.; Shayo, C.; Monczor, F.; Fernandez, N.; Baldi, A.; De Kimpe, N.; Rossi, J.; Debenedetti, S.; Davio, C.
Cancer Lett.
2004,
210, 179–188]. These promising findings prompted us to investigate the anti-leukemia activity of a broader range of related polyoxygenated coumarins. Twenty related natural or synthetically prepared coumarins, including a range of 5-substituted ayapin derivatives which have become easy accessible via newly developed synthesis methods, were evaluated, where treatments with 5-(2,3-dihydroxy-3-methylbutoxy)-6,7-methylenedioxycoumarin (
D-
3) and 5-(2-hydroxy-3-methoxy-3-methylbutoxy)-6,7-methylenedioxycoumarin (
D-
2) were able to inhibit the cell growth and induce the differentiation of U-937 cells after 48
h treatment. These results provide insight into the correlation between some structural properties of polyoxygenated coumarins and their in vitro leukemic differentiation activity. |
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ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2009.08.002 |