Design, synthesis, and analysis of antiproliferative and apoptosis-inducing activities of nitrile derivatives containing a benzofuran scaffold: EGFR inhibition assay and molecular modelling study

New cyanobenzofurans derivatives 2-12 were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC50 = 4.17-8.87 and 5.5-11.2 mu M, respectively). Compounds 2 and 8 exhibited broad-spectrum activity against HePG2 (IC50 = 16.08-23.67 mu M), HCT-116 (IC50 = 8.81-13.85 mu M), and MCF-7 (IC50 = 8.36-17.28 mu M) cell lines. Compounds 2, 3, 8, 10, and 11 were tested as EGFR-TK inhibitors to demonstrate their possible anti-tumour mechanism compared to gefitinib (IC50 = 0.90 mu M). Compounds 2, 3, 10, and 11 displayed significant EGFR TK inhibitory activity with IC50 of 0.81-1.12 mu M. Compounds 3 and 11 induced apoptosis at the Pre-G phase and cell cycle arrest at the G2/M phase. They also increased the level of caspase-3 by 5.7- and 7.3-fold, respectively. The molecular docking analysis of compounds 2, 3, 10, and 11 indicated that they could bind to the active site of EGFR TK.