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Research aimed at developing potent di-indol-3-yl disulphides for cancer diseases makes use of various theoretical techniques to evaluate the drug-likeness parameters and the mode of action. A drug-likeness filter helps evaluate the therapeutic potency of four  bis -indole derivatives, structurally related to 3,3′-methanediyl- bis -indole (DIM) but having the S-S instead of the methylene linker and showing a high inhibitory impact on the variants of cancer cell lines (among them HL-60 and DU-145). Based on  in vitro  experimental results for their close analogues, a correlation was found between the epidermal growth factor receptor kinase (EGFR) inhibition and the theoretical energy of complexation. Docking studies of ligands followed by molecular dynamics were performed at the ATP-binding site of EGFR tyrosine kinase to scrutinize the inhibition of the di-indol-3-yl disulphides at a molecular level. Derivatives with bromine or iodine substituents at C-5 positions of the indole moieties made strong complexes by interaction with the most important hinge region residues Met-793 and Cys-733. The inhibition model for EGFR kinase and the proposed procedures can be very informative in the biological testing of selected  bis -indoles and may be useful for future research on effective inhibitors for the treatment of EGFR-related cancer. Communicated by Ramaswamy H. Sarma

Theoretical evaluation of EGFR kinase inhibition and toxicity of di-indol-3-yl disulphides with anti-cancer potency