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

Abstract

New cyanobenzofurans derivatives 2-12 were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC 50 ¼ 4.17-8.87 and 5.5-11.2 mM, respectively). Compounds 2 and 8 exhibited broad-spectrum activity against HePG2 (IC 50 ¼ 16.08-23.67 mM), HCT-116 (IC 50 ¼ 8.81-13.85 mM), and MCF-7 (IC 50 ¼ 8.36-17.28 mM) 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 (IC 50 5 0.90 mM). Compounds 2, 3, 10, and 11 displayed significant EGFR TK inhibitory activity with IC 50 of 0.81-1.12 mM. 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.

Synthesis, photophysical properties, anticancer evaluation, and molecular docking studies of new pyrimidine linked 4‐arylidene‐thiazolidin‐4‐ones as potent anticancer agents

“…As an EGFR tyrosine kinase (EGFR‐TK) functions as a tyrosine kinase receptor, playing a critical role in regulating several biological functions such as cell movement, attachment, control, blood vessel formation, programmed cell death, and the spread of cancer cells [38]. Importantly, a higher than normal presence of these receptors is observed in different types of cancer cells, including those of the colon, ovaries, prostate, and breast [39]. The results are recorded in Table 5.…”

“…and the spread of cancer cells [38]. Importantly, a higher than normal presence of these receptors is observed in different types of cancer cells, including those of the colon, ovaries, prostate, and breast [39].…”

Anticancer therapeutic potential of benzofuran scaffolds

“…Molecular docking results of 26 showed good tting and suitable interactions with the key amino residues in the binding site of the EGFR kinase, where the cyano group enabled the hydrogen bonding interactions with the Met769 amino acid and benzofuran moiety showed van der Waals interactions with the EGFR binding site. 48 The 2-acetyl-7-phenylaminobenzofuran hybrid 27 was reported as a promising STAT3 inhibitor (signal transducer and activator of transcription 3). Interestingly, compound 27 displayed very potent antiproliferation activity against MDA-MB-468 cells with IC 50 value of 0.16 mM.…”

“…Molecular docking results of 26 showed good fitting and suitable interactions with the key amino residues in the binding site of the EGFR kinase, where the cyano group enabled the hydrogen bonding interactions with the Met769 amino acid and benzofuran moiety showed van der Waals interactions with the EGFR binding site. 48 …”