新型异甜菊醇融合吡唑啉和吡唑类化合物的设计与立体选择性合成及其作为潜在抗癌药物的研究。
Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents.
机构信息
New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, No. 100, KeXue Avenue, Zhengzhou, Henan 450001, China.
出版信息
Eur J Med Chem. 2013 Jul;65:70-82. doi: 10.1016/j.ejmech.2013.04.044. Epub 2013 May 2.
Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 μM against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 μM, respectively).
通过分子内 1,3-偶极环加成和缩合反应，分别简便地合成了两个系列新型甜菊醇融合吡唑啉和吡唑衍生物。所有化合物均通过 NMR、IR 和 HRMS 光谱进行了表征。化合物 9b、10、11a 和 11v 的立体化学结构通过 X 射线晶体学分析进一步得到证实。对结构相关的吡唑啉和吡唑衍生物进行了体外抗增殖活性测试，选用了四种人恶性细胞系（SGC 7901、A549、Raji 和 HeLa）：我们的结果表明，甜菊醇融合吡唑衍生物表现出显著的细胞毒性。其中，2,4-二-Cl-苯基吡唑衍生物 11t 对 SGC 7901、A549、Raji 和 HeLa 的细胞毒性更强，IC50 值分别为 2.71、3.18、1.09 和 13.52 μM，而顺铂（IC50 值分别为 7.56、17.78、17.32 和 14.31 μM）。
Zotero 插件