2-Phenylbenzo[b]furans: Synthesis and promoting activity on estrogen biosynthesis

Bioorg Med Chem Lett. 2016 Nov 15;26(22):5497-5500. doi: 10.1016/j.bmcl.2016.10.013. Epub 2016 Oct 8.

Abstract

Estrogen biosynthesis is pivotal to many physiological processes of human. Aberrant estrogen level is closely related to a variety of diseases, including breast cancer and osteoporosis. Previously we found that 2-phenylbenzo[b]furan glycosides could promote estrogen biosynthesis. To find high active 2-phenylbenzo[b]furans, fifty-four 2-phenylbenzo[b]furans were prepared via four strategies according to corresponding substrate scopes. Biological evaluation in HEK293A cells showed that some compounds exhibited promotive activity on estrogen biosynthesis. 2-(4-Chlorophenyl)-7-methoxybenzo[b]furan possessed the highest activity with EC50 value of 14.68μM. Furthermore, these compounds did not affect aromatase expression in HEK292A cells, indicating that these 2-phenylbenzo[b]furans might enhance estrogen biosynthesis via directly allosteric regulation of aromatase or indirectly via posttranslational modification.

Keywords: 2-Phenylbenzo[b]furan; Decarboxylative coupling; Estrogen biosynthesis; McMurry reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / metabolism
  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry*
  • Benzene Derivatives / pharmacology*
  • Biosynthetic Pathways / drug effects
  • Estrogens / agonists*
  • Estrogens / metabolism*
  • Furans / chemical synthesis
  • Furans / chemistry*
  • Furans / pharmacology*
  • HEK293 Cells
  • Humans

Substances

  • Benzene Derivatives
  • Estrogens
  • Furans
  • Aromatase