Synthesis and biological evaluation of the salicylamide and salicylic acid derivatives as anti-estrogen agents

Med Chem. 2012 May;8(3):481-90. doi: 10.2174/1573406411208030481.

Abstract

Alkylphenols have xenoestrogenic activity, which mimic the action of physiological estrogens and these mimicking activities are mainly mediated by nongenomic pathway. Nongenomic pathway plays a pivotal role in breast, endometrial and ovarian cancers' growth and development. In this study, various alkylphenol derivatives were prepared and screened for their anti-uterotrophic and uterotrophic activity. Among these compounds, 2-hydroxy-5-nonanoylbenzamide (compound 1b) showed 93.99% inhibitory activity in the anti-uterotrophic test performed, and was found inactive in the uterotrophic activity test. Moreover, all test compounds were examined for the effect on uterine histopathological changes, and plasma 17β-estradiol (E2) level. Compound 1b was also tested for in vitro anti-cancer activity against ER+, human breast cancer cell line MCF-7, and it reduced cell viability to 74.01% at 50 nM concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Estrogens / metabolism*
  • Female
  • Humans
  • Molecular Structure
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / metabolism
  • Salicylamides / chemistry*
  • Salicylamides / pharmacology*
  • Salicylic Acid / chemistry*
  • Salicylic Acid / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Uterus / drug effects*
  • Uterus / pathology

Substances

  • Antineoplastic Agents
  • Estrogens
  • Receptors, Estrogen
  • Salicylamides
  • salicylamide
  • Salicylic Acid