Synthesis, Characterisation, Molecular Docking Studies and Biological Evaluation of Novel Benzothiazole Derivatives as EGFR Inhibitors for Anti-breast Cancer Agents

Abstract

Novel (2-anilino-N-(4,6-dimethyl-1,3-Benzosulfonazol-2-yl) ethanamide derivatives were synthesized and characterized by spectroscopy methods. All the compounds assessed for in-vitro antimicrobial activities on three strains are S. aureus, S. epidermis and E. coli by using disc plate method (25 μg/mL). Compounds 5a-5j showed good to excellent antimicrobial activity for three different strains compared to standard ciprofloxacin. Further screened by in-vitro cytotoxic activity against MCF-7 cell lines. Some compounds were 5i, 5c, 5b,5d and 5i showed high cytotoxic activities of IC50 values 73, 53,37,32 and 24 μg/mL, reference drug as Gefitinib against MCF-7 cell lines and MCF-12A. Further carried out docking studies using Schrodinger software to analyze the orientations, interactions and binding modes of these derivatives at the adenine -5-triphosphate binding site of EGFR (PDB ID: 2ITY), which indicated that the ligands show good interactions with active site residues in this structural benzothiazole class, and are considered lead compounds for further development as anti-breast cancer drugs