Abstract

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 µM, respectively). Compounds 2 and 8 exhibited broad-spectrum activity against HePG2 (IC₅₀ = 16.08–23.67 µM), HCT-116 (IC₅₀ = 8.81–13.85 µM), and MCF-7 (IC₅₀ = 8.36–17.28 µM) 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 µM). Compounds 2, 3, 10, and 11 displayed significant EGFR TK inhibitory activity with IC₅₀ of 0.81–1.12 µM. 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.

摘要

合成了新的氰基苯并呋喃衍生物2-12，并与多柔比星和阿法替尼（IC ₅₀ = 4.17-8.87 和 5.5-11.2 µM，分别）相比，检查了它们的抗增殖活性。化合物2和8对 HePG2 (IC ₅₀ = 16.08–23.67 µM)、HCT-116 (IC ₅₀ = 8.81–13.85 µM) 和 MCF-7 (IC ₅₀ = 8.36–17.28 µM) 细胞系表现出广谱活性。化合物2，3，8，10，和11测试了作为EGFR-TK抑制剂相比吉非替尼以证明它们可能的抗肿瘤机制（IC ₅₀ =0.90 微米）。化合物2，3，10，和11显示显著EGFR TK抑制活性IC ₅₀ 0.81-1.12微米。化合物3和11在 Pre-G 期诱导细胞凋亡，在 G2/M 期诱导细胞周期停滞。他们还将 caspase-3 的水平分别提高了 5.7 倍和 7.3 倍。化合物的分子对接分析2，3，10，和11表示，它们可以结合EGFR TK的活性位点。