设计、合成及新型苯并呋喃杂合体的计算研究：作为双重 PI3K/VEGFR2 抑制剂的癌症靶向治疗药物。
Design, synthesis and computational study of new benzofuran hybrids as dual PI3K/VEGFR2 inhibitors targeting cancer.
机构信息
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.
Faculty of Pharmacy, New Mansoura University, P.O. Box 35712, New Mansoura, Egypt.
出版信息
Sci Rep. 2022 Oct 12;12(1):17104. doi: 10.1038/s41598-022-21277-2.
Design and synthesis of a new series of benzofuran derivatives has been performed. H-NMR, C-NMR, elemental analysis, and IR were used to confirm the structures of the produced compounds. Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), epithelioid carcinoma cervical cancer (Hela), and human prostate cancer are used to test anticancer activity (PC3). In compared to DOX (4.17-8.87 µM), Compound 8 demonstrated the highest activity against HePG and PC3 cell lines, with an IC range of 11-17 µM. Compound 8 inhibited PI3K and VEGFR-2 with IC values of 2.21 and 68 nM, respectively, compared to 6.18 nM for compound LY294002 and 31.2 nM for compound sorafenib as PI3K and VEGFR-2 reference inhibitors, selectively. The molecular docking and binding affinity of the generated compounds were estimated and studied computationally utilizing molecular operating environment software as a PI3K and VEGFR-2 inhibitor (MOE). In conclusion, compound 8 exhibited significant action against hepatocellular and cervical cancer cell lines. Mechanistic study showed that it had a dual inhibitory effect against PI3K and VEGFR-2.
已经进行了一系列新型苯并呋喃衍生物的设计和合成。采用 H-NMR、C-NMR、元素分析和 IR 来确认所产生化合物的结构。采用肝癌（HePG2）、乳腺癌（MCF-7）、宫颈上皮样癌细胞癌（Hela）和人前列腺癌细胞（PC3）来测试抗癌活性。与 DOX（4.17-8.87 μM）相比，化合物 8 对 HePG 和 PC3 细胞系表现出最高的活性，IC 范围为 11-17 μM。与 PI3K 和 VEGFR-2 的参考抑制剂化合物 LY294002（6.18 nM）和化合物索拉非尼（31.2 nM）相比，化合物 8 对 PI3K 和 VEGFR-2 的抑制作用分别为 IC 值 2.21 和 68 nM。生成的化合物的分子对接和结合亲和力使用分子操作环境软件（MOE）进行了计算和研究。总之，化合物 8 对肝癌和宫颈癌细胞系表现出显著的作用。机制研究表明，它对 PI3K 和 VEGFR-2 具有双重抑制作用。
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