Title:The Efficient Activity of Glabridin and its Derivatives Against EGFRmediated
Inhibition of Breast Cancer
Volume: 31
Issue: 5
关键词:
乳腺癌，酚类化合物，光甘草定，信号通路，表皮生长因子受体，分子动力学模拟。
摘要:
Background: Breast cancer (BC) is one of the most typical causes of cancer
death in women worldwide. Activated epidermal growth factor receptor (EGFR) signaling
has been increasingly associated with BC development and resistance to cytotoxic
drugs. Due to its significant association with tumour metastasis and poor prognosis,
EGFR-mediated signaling has emerged as an attractive therapeutic target in BC. Mainly
in all BC cases, mutant cells over-expresses EGFR. Certain synthetic drugs are already
used to inhibit the EGFR-mediated pathway to cease metastasis, with several phytocompounds
also revealing great chemopreventive activities.
Methods: This study used chemo-informatics to predict an effective drug from some selected
phytocompounds. The synthetic drugs and the organic compounds were individually
screened for their binding affinities, with EGFR being the target protein using molecular
docking techniques.
Results: The binding energies were compared to those of synthetic drugs. Among phytocompounds,
Glabridin (phytocompound of Glycyrrhiza glabra) manifested the best dock
value of -7.63 Kcal/mol, comparable to that of the highly effective anti-cancer drug Afatinib.
The glabridin derivatives also exhibited comparable dock values.
Conclusion: The AMES properties deciphered the non-toxic features of the predicted
compound. Pharmacophore modeling and in silico cytotoxicity predictions also exhibited
a superior result assuring their drug likeliness. Therefore, Glabridin can be conceived as
a promising therapeutic method to inhibit EGFR-mediated BC.
