School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, PR China.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Bioorg Chem. 2022 Sep;126:105922. doi: 10.1016/j.bioorg.2022.105922. Epub 2022 Jun 2.
Indazole is a significant class of heterocyclic compounds with a wide range of biological activity. We display here the synthesis and biological evaluation of a novel series of indazole derivatives 6a-v, which are differently substituted at the 6-position of the indazole moiety. The antiproliferative activity of compounds 6a-v was tested against four human cancer cell lines, using the MTT assay and doxorubicin as the reference drug. Compounds 6f, 6i, 6j, 6 s, and 6n were the most effective synthesized derivatives, with GI values of 0.77, 0.86, 1.05, 1.05, and 1.07 µM, respectively, against the 4 cell lines, in comparison to the control doxorubicin (GI = 1.10 µM). Compounds 6f, 6i, 6j, and 6 s the most potent derivatives as antiproliferative agents, displayed the utmost inhibitory activity against EGFR, and CDK2 and c-Met. Compounds 6f, 6n, and 6 s induced apoptosis through cytochrome C overexpression and activation of the intrinsic apoptotic pathway generated by the investigated compounds.
吲唑是一类具有广泛生物活性的重要杂环化合物。我们在这里展示了一系列新型吲唑衍生物 6a-v 的合成和生物评价，它们在吲唑部分的 6 位具有不同的取代基。我们使用 MTT 法和阿霉素作为参考药物，测试了化合物 6a-v 对四种人类癌细胞系的增殖抑制活性。化合物 6f、6i、6j、6s 和 6n 是合成的最有效的衍生物，它们对 4 种细胞系的 GI 值分别为 0.77、0.86、1.05、1.05 和 1.07µM，与对照阿霉素（GI=1.10µM）相比。作为增殖抑制剂，化合物 6f、6i、6j 和 6s 是最有效的衍生物，对 EGFR、CDK2 和 c-Met 表现出最大的抑制活性。化合物 6f、6n 和 6s 通过细胞色素 C 过表达和所研究化合物产生的内在凋亡途径的激活诱导细胞凋亡。
