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

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 derivat...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/80917
Acceso en línea:http://hdl.handle.net/11336/80917
Access Level:acceso abierto
Palabra clave:Apoptosis
Catechol
Coumarins
Differentiating Activity
Leukemia
Selective Cytotoxicity
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario: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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