title: Toward establishing structure-activity relationships for oxygenated coumarins as differentiation inducers of promonocytic leukemic cells.
abstract: 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.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina.
authors.forename: María E
authors.initials: ME
authors.lastname: Riveiro
authors.forename: Dominick
authors.initials: D
authors.lastname: Maes
authors.forename: Ramiro
authors.initials: R
authors.lastname: Vázquez
authors.forename: Monica
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Sven
authors.initials: S
authors.lastname: Mangelinckx
authors.forename: Jan
authors.initials: J
authors.lastname: Jacobs
authors.forename: Silvia
authors.initials: S
authors.lastname: Debenedetti
authors.forename: Carina
authors.initials: C
authors.lastname: Shayo
authors.forename: Norbert
authors.initials: N
authors.lastname: De Kimpe
authors.forename: Carlos
authors.initials: C
authors.lastname: Davio
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D010100:Oxygen / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D010100:Oxygen