info:eu-repo/semantics/article
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
Fecha
2012-09Registro en:
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
0968-0896
CONICET Digital
CONICET
Autor
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
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.