Evaluation of synthesized coumarin derivatives on aromatase inhibitory activity

Bioorg Med Chem Lett. 2017 Jun 15;27(12):2645-2649. doi: 10.1016/j.bmcl.2017.01.062. Epub 2017 Jan 25.

Abstract

In women across the world, the most common type of cancer is breast cancer. Among medical treatments, endocrine therapy based on aromatase inhibitors (AI) is expected to be effective against not only post-menopausal but also pre-menopausal breast cancer. In this study, we examined the structure-activity relationship between the aromatase inhibitory effects of 7-diethylaminocoumarin derivatives with a substituent at position 3 and coumarin derivatives with a substituent at position 7. Consequently, we found that 7-(pyridin-3-yl)coumarin (IC50 values 30.3nM) and 7,7'-diethylamino-3,3'-biscoumarin (28.7nM) are the most potent inhibitors of aromatase. These inhibitors were found to be comparable to the existing CYP19 inhibitor exemestane (42.5nM).

Keywords: Aromatase; Breast cancer; CYP19; Coumarin; Inhibitor; Oxazole; Pyridine; Thiazole.

MeSH terms

  • Aromatase / metabolism*
  • Aromatase Inhibitors / chemical synthesis
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / pharmacology*
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Aromatase Inhibitors
  • Coumarins
  • coumarin
  • Aromatase