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 were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC = 4.17-8.87 and 5.5-11.2 µM, respectively). Compounds and exhibited broad-spectrum activity against HePG2 (IC = 16.08-23.67 µM), HCT-116 (IC = 8.81-13.85 µM), and MCF-7 (IC = 8.36-17.28 µM) cell lines. Compounds , , , , and were tested as EGFR-TK inhibitors to demonstrate their possible anti-tumour mechanism compared to gefitinib (IC 0.90 µM). Compounds , , , and displayed significant EGFR TK inhibitory activity with IC of 0.81-1.12 µM. Compounds and 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 , , , and indicated that they could bind to the active site of EGFR TK.