Development of Photoswitchable Estrogen Receptor Ligands

Chem Pharm Bull (Tokyo). 2020;68(4):398-402. doi: 10.1248/cpb.c19-01108.

Abstract

Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on their conformational change by photo-irradiation. Previously, we have reported several types of selective estrogen receptor (ER) modulators based on diphenylmethane skeleton. To develop novel photopharmacological reagents, we designed and synthesized a set of ER ligands based on azobenzene skeleton, which can switch its conformation following UV irradiation. Our results showed that after UV irradiation, the Z-form of the synthesized compound 9 interacted with ERα, with a KD value of 2.5 µM, whereas the E-form of compound 9 did not bind ability to ERα at 10 µM.

Keywords: diazo moiety; estrogen receptor; fluorescent polarization assay; photopharmacology.

MeSH terms

  • Azo Compounds / chemical synthesis
  • Azo Compounds / chemistry
  • Azo Compounds / pharmacology*
  • Fluorescence Polarization
  • Humans
  • Ligands
  • Molecular Structure
  • Photochemical Processes
  • Receptors, Estrogen / antagonists & inhibitors*
  • Receptors, Estrogen / metabolism
  • Selective Estrogen Receptor Modulators / chemical synthesis
  • Selective Estrogen Receptor Modulators / chemistry
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Ultraviolet Rays

Substances

  • Azo Compounds
  • Ligands
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • azobenzene