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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Bibliographic Details
Authors: 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
Format: article
Status:Published version
Publication Date:2012
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/80917
Online Access:http://hdl.handle.net/11336/80917
Access Level:Open access
Keyword:Apoptosis
Catechol
Coumarins
Differentiating Activity
Leukemia
Selective Cytotoxicity
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Description
Summary: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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