Artículo
Structure-anti-leukemic activity relationship study of ortho- dihydroxycoumarins in U-937 cells: Key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action
Vazquez, Ramiro
; Riveiro, Maria Eugenia
; Vermeulen, Elba Monica
; Alonso, Eliana; Mondillo, Carolina
; Facorro, Graciela; Piehl, Lidia Leonor; Gomez, Natalia
; Moglioni, Albertina Gladys
; Fernandez, Natalia Cristina
; Baldi, Alberto
; Shayo, Carina Claudia
; Davio, Carlos Alberto
Fecha de publicación:
09/2012
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Bioorganic & Medicinal Chemistry
ISSN:
0968-0896
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Previous studies indicated the need of at least one phenolic hydroxyl group in the coumarin core for induction of cytotoxicity in different cell lines. Herein, we present an exhaustive structure-activity relationship study including ortho-dihydroxycoumarins (o-DHC) derivatives, cinnamic acid derivatives (as open-chain coumarin analogues) and 1,2-pyrones (representative of the δ-lactone ring of the coumarin core), carried out to further identify the structural features of o-DHC required to induce leukemic cell differentiation and apoptosis in U-937 cells. Our results show for the first time that the δ-lactone ring positively influences the aforementioned biological effects, by conferring greater potency to compounds with an intact coumarin nucleus. Most tellingly, we reveal herein the crucial role of this molecular portion in determining the selective toxicity that o-DHC show for leukemic cells over normal blood cells. From a pharmacological perspective, our findings point out that o-DHC may be useful prototypes for the development of novel chemotherapeutic agents.
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Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IMEX)
Articulos de INST.DE MEDICINA EXPERIMENTAL
Articulos de INST.DE MEDICINA EXPERIMENTAL
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Vazquez, Ramiro; Riveiro, Maria Eugenia; Vermeulen, Elba Monica; Alonso, Eliana; Mondillo, Carolina; et al.; Structure-anti-leukemic activity relationship study of ortho- dihydroxycoumarins in U-937 cells: Key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 20; 18; 9-2012; 5537-5549
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