New scaffolds for the design of selective estrogen receptor modulators

Sonsoles Martín-Santamaría; José Juan Rodríguez; Sonia De Pascual-Teresa; Sandra Gordon; Martin Bengtsson; Ignacio Garrido-Laguna; Belén Rubio-Viqueira; Pedro P. López-Casas; Manuel Hidalgo; Beatriz De Pascual-Teresa; Ana Ramos

doi:10.1039/b806918b

New scaffolds for the design of selective estrogen receptor modulators

Sonsoles Martín-Santamaría, José Juan Rodríguez, Sonia De Pascual-Teresa, Sandra Gordon, Martin Bengtsson, Ignacio Garrido-Laguna, Belén Rubio-Viqueira, Pedro P. López-Casas, Manuel Hidalgo, Beatriz De Pascual-Teresa, Ana Ramos

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

In the present work we report the synthesis of four new ER ligands which can be used as scaffolds for the introduction of the basic side chains necessary for antiestrogenic activity. Affinities and agonist/antagonist characterization of the ligands for both ERα and ERβ have been determined in a competitive radioligand assay, and in an in vitro coactivator recruitment functional assay, respectively. Molecular modelling techniques have been used in order to rationalize the experimental results. Compound 2 is reported as a novel ERβ-agonist/ERα-antagonist. Two compounds show an interesting antitumour profile towards two pancreatic cancer cell lines and have been selected for in vivo assays.

Original language	English (US)
Pages (from-to)	3486-3496
Number of pages	11
Journal	Organic and Biomolecular Chemistry
Volume	6
Issue number	19
DOIs	https://doi.org/10.1039/b806918b
State	Published - 2008
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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abstract = "In the present work we report the synthesis of four new ER ligands which can be used as scaffolds for the introduction of the basic side chains necessary for antiestrogenic activity. Affinities and agonist/antagonist characterization of the ligands for both ERα and ERβ have been determined in a competitive radioligand assay, and in an in vitro coactivator recruitment functional assay, respectively. Molecular modelling techniques have been used in order to rationalize the experimental results. Compound 2 is reported as a novel ERβ-agonist/ERα-antagonist. Two compounds show an interesting antitumour profile towards two pancreatic cancer cell lines and have been selected for in vivo assays.",

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AU - Martín-Santamaría, Sonsoles

AU - Rodríguez, José Juan

AU - De Pascual-Teresa, Sonia

AU - Gordon, Sandra

AU - Bengtsson, Martin

AU - Garrido-Laguna, Ignacio

AU - Rubio-Viqueira, Belén

AU - López-Casas, Pedro P.

AU - Hidalgo, Manuel

AU - De Pascual-Teresa, Beatriz

AU - Ramos, Ana

PY - 2008

Y1 - 2008

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AB - In the present work we report the synthesis of four new ER ligands which can be used as scaffolds for the introduction of the basic side chains necessary for antiestrogenic activity. Affinities and agonist/antagonist characterization of the ligands for both ERα and ERβ have been determined in a competitive radioligand assay, and in an in vitro coactivator recruitment functional assay, respectively. Molecular modelling techniques have been used in order to rationalize the experimental results. Compound 2 is reported as a novel ERβ-agonist/ERα-antagonist. Two compounds show an interesting antitumour profile towards two pancreatic cancer cell lines and have been selected for in vivo assays.

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New scaffolds for the design of selective estrogen receptor modulators

Abstract

ASJC Scopus subject areas

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