title: Investigation of fluorinated and bifunctionalized 3-phenylchroman-4-one (isoflavanone) aromatase inhibitors.
abstract: Fluorinated isoflavanones and bifunctionalized isoflavanones were synthesized through a one-step gold(I)-catalyzed annulation reaction. These compounds were evaluated for their in vitro inhibitory activities against aromatase in a fluorescence-based enzymatic assay. Selected compounds were tested for their anti-proliferative effects on human breast cancer cell line MCF-7. Compounds 6-methoxy-3-(pyridin-3-yl)chroman-4-one (3c) and 6-fluoro-3-(pyridin-3-yl)chroman-4-one (3e) were identified as the most potent aromatase inhibitors with IC₅₀ values of 2.5 μM and 0.8 μM. Therefore, these compounds have great potential for the development of pharmaceutical agents against breast cancer.
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
authors.forename: Erica
authors.initials: E
authors.lastname: Amato
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
authors.forename: Tony
authors.initials: T
authors.lastname: Bankemper
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kidney
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
authors.forename: Thuy
authors.initials: T
authors.lastname: Do
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
authors.forename: Alma
authors.initials: A
authors.lastname: Onate
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, United States.
authors.forename: Fathima Shazna
authors.initials: FS
authors.lastname: Thowfeik
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, United States.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Merino
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
authors.forename: Stefan
authors.initials: S
authors.lastname: Paula
authors.affiliation: Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States. Electronic address: mal1@nku.edu.
authors.forename: Lili
authors.initials: L
authors.lastname: Ma
mesh_terms: D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*
chemical_list: D047072:Aromatase Inhibitors; D007529:Isoflavones; C065753:isoflavanone
keywords: AIs; Arg 115; Aromatase inhibitors; Asp 309; Breast cancer; CYP19; Estrogen; Fluorine; Functional groups; HPLC; Ile 133; Isoflavanones; Leu 477; MS; NMR; NSAIs; Phe 221; SERMs; Thr 310; Trp 224; Val 370; arginine 115; aromatase inhibitors; aspartic acid 309; cytochrome P450 aromatase; high performance liquid chromatography; isoleucine 133; leucine 477; mass spectrometry; non-steroidal aromatase inhibitors; nuclear magnetic resonance; phenylalanine 221; selective estrogen receptor modulators; threonine 310; tryptophan 224; valine 370