In silico and In vitro studies of EGFR kinase and Anilide derivatives as inhibitors against Breast Cancer

Abstract

The benzanilide scaffold is well known for its biological activities, such as antifungal, antibacterial, herbicide, and anti-tumor activity. Benzanilides with halogen substitution were computationally designed and screened against EGFR kinase, with erlotinib as a reference compound, using molecular docking. Two compounds were synthesized by the Schotten-Baumann reaction and confirmed based on FT-IR spectrophotometry, TLC, and sharp, narrow-range melting point analyses. The synthesized compounds were tested for antiproliferative activity and acute toxicity using the MTT assay with the (MCF-7) human breast cancer cell line. The effect of the compounds on non-cancerous cells in the human body was tested using blood lymphocytes. The mechanism of action evaluated by an in vitro cytotoxicity study revealed IC50 values of compound A = 75.54 ± 4.7 μM and compound B = 178.5 ± 9.0 μM (mean ± SEM, n = 3), showing promising growth-inhibitory cytotoxic actions with increasing concentrations against EGFR in breast cancer. Docking studies revealed that synthesized compounds interacted with a similar enzyme and ATP binding site of EGFR-TK in the reference drug erlotinib, along with additional strong interactions indicating efficacy and potency. To predict better tolerability and late failure, toxicity predictions were made for the synthesized compounds. Therefore, this research aimed to demonstrate the activity of several promising benzanilide molecules.