Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of Cannabis sativa in Breast Cancer

Recent Pat Anticancer Drug Discov. 2021;16(2):273-284. doi: 10.2174/1574892816666210201115359.


Background: Breast Cancer (BC), a common fatal disease and the deadliest cancer next to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy is marked by targeting the activities of some receptors such as Estrogen Receptor alpha (ER-α). At present, one of the most commonly used and approved marketed therapeutic drugs for BC is tamoxifen. Despite the short-term success of tamoxifen usage, its long time treatment has been associated with significant side effects. Therefore, there is a pressing need for the development of novel anti-estrogens for the prevention and treatment of BC.

Objective: In this study, we evaluate the inhibitory effect of Cannabis sativa phytoconstituents on ER-α.

Methods: Glide and induced fit docking followed by ADME, automated QSAR and binding free energy (Δ>Gbind) studies were used to evaluate anti-breast cancer and ER-α inhibitory activity of Cannabis sativa, which has been reported to be effective in inhibiting breast cancer cell proliferation.

Results: Phyto-constituents of Cannabis sativa possess lower docking scores and good ΔGbind when compared to that of tamoxifen. ADME and AutoQSAR studies revealed that our lead compounds demonstrated the properties required to make them promising therapeutic agents.

Conclusion: The results of this study suggest that naringenin, dihydroresveratrol, baicalein, apigenin and cannabitriol could have relatively better inhibitory activity than tamoxifen and could be a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo and/or in vitro assays could be conducted to verify the ability of these compounds.

Keywords: ADME; AutoQSAR; MM-GBSA.; breast cancer; cancer; docking; estrogen; induced-fit docking.

Publication types

  • Comparative Study

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Cannabis / chemistry*
  • Estrogen Antagonists / chemistry
  • Estrogen Antagonists / pharmacology
  • Estrogen Receptor alpha / antagonists & inhibitors*
  • Female
  • Humans
  • Molecular Docking Simulation
  • Patents as Topic
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Quantitative Structure-Activity Relationship
  • Tamoxifen / pharmacology


  • ESR1 protein, human
  • Estrogen Antagonists
  • Estrogen Receptor alpha
  • Plant Preparations
  • Tamoxifen