Investigation of fluorinated and bifunctionalized 3-phenylchroman-4-one (isoflavanone) aromatase inhibitors

  • Bioorg Med Chem. 2014 Jan 1;22(1):126-34. doi: 10.1016/j.bmc.2013.11.045.
Erica Amato  1 ,  Tony Bankemper  1 ,  Rebecca Kidney  1 ,  Thuy Do  1 ,  Alma Onate  1 ,  Fathima Shazna Thowfeik  2 ,  Edward J Merino  2 ,  Stefan Paula  1 ,  Lili Ma  3
Affiliations
  • 1. Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
  • 2. Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, United States.
  • 3. Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States. Electronic address: [email protected].
PMID: 24345481 DOI: 10.1016/j.bmc.2013.11.045
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.

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.