title: Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and Its Analogues.
abstract: The natural product ferutinin was shown to act as an agonist to estrogen receptor ERα and agonist/antagonist to ERβ featuring a weak antiproliferative activity toward breast cancer cells. To enhance this activity, ferutinin analogues were synthesized by esterification of jaeschkenadiol with different acids. These compounds were assayed for their in vitro antiproliferative activity against estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cell lines. Among the compounds, 3c' exhibited a potent inhibitory selective activity against MCF-7 with IC50 value of 1 μM. Docking simulation of 3c' in the ligand binding domain of the ERs indicated a potential antagonism interaction with both ER subtypes. Functional assay showed that 3c' binds as an antagonist to ERα protein while ferutinin acts as an agonist.
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Sciences II/EDST, Lebanese University, Jdeidet el Metn - Fanar, Lebanon.|Laboratoire de Synthèse et Physicochimie des Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse Cédex, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Safi
authors.affiliation: Laboratoire de Synthèse et Physicochimie des Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse Cédex, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Rodriguez
authors.affiliation: Cancer and Metabolism Research Laboratory, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Georges
authors.initials: G
authors.lastname: Hilal
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Sciences II/EDST, Lebanese University, Jdeidet el Metn - Fanar, Lebanon.
authors.forename: Mona
authors.initials: M
authors.lastname: Diab-Assaf
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Sciences II/EDST, Lebanese University, Jdeidet el Metn - Fanar, Lebanon.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Diab
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Marwan
authors.initials: M
authors.lastname: El-Sabban
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Sciences II/EDST, Lebanese University, Jdeidet el Metn - Fanar, Lebanon.
authors.forename: Fadia
authors.initials: F
authors.lastname: Najjar
authors.affiliation: Laboratoire de Synthèse et Physicochimie des Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse Cédex, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Delfourne
mesh_terms: D001565:Benzoates / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D045744:Cell Line, Tumor; D003508:Cycloheptanes / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D012717:Sesquiterpenes / Q000378:metabolism*; D013055:Spectrophotometry, Infrared
chemical_list: D001565:Benzoates; D001643:Bridged Bicyclo Compounds; D003508:Cycloheptanes; D012717:Sesquiterpenes; C111068:4-oxy-6-(4-oxybezoyloxy)dauc-8,9-en
keywords: Ferula hermonis; antitumor agents; breast cancer; estrogen receptors; ferutinin; jaeschkenadiol; molecular docking