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</i>) 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</i> 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.
Keywords: Breast cancer; epidermal growth factor receptor; glabridin; molecular dynamics simulation; phenolic compounds; signaling pathways.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.