基于新型香豆素/吡唑肟类化合物的优异抗肿瘤和抗转移活性。
Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids.
机构信息
College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, People's Republic of China; School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China.
School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, People's Republic of China.
出版信息
Eur J Med Chem. 2019 Mar 15;166:470-479. doi: 10.1016/j.ejmech.2019.01.070. Epub 2019 Jan 30.
A series of hybrids 10a-v based on coumarin/pyrazole oxime have been synthesized, and exhibit good to excellent antitumor activities. Compound 10n has shown remarkable anticancer effect on SMMC-7721 cells (IC = 2.08 μM), which is considerably lower than 5-FU (IC = 37.8 μM) and similar to ADM (IC = 2.67 μM), with little effect on normal hepatic cells LO2. Notably, the suppression experiments of metastatic activities reveal that 10n also displays significant anti-metastasis effects through inhibiting cell migration and invasion in highly metastatic SMMC-7721 cell line, and dose-dependently reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) procedure better than ADM. Finally, 10n also possesses low acute toxicity and potent tumor growth inhibitory property against SMMC-7721 cell lines in vivo. Our findings suggest that novel coumarin/pyrazole oxime hybrids are promising therapeutic agent candidates for further research.
已经合成了一系列基于香豆素/吡唑肟的杂种 10a-v，并表现出良好到优异的抗肿瘤活性。化合物 10n 对 SMMC-7721 细胞表现出显著的抗癌作用（IC=2.08μM），明显低于 5-FU（IC=37.8μM），与 ADM（IC=2.67μM）相似，对正常肝细胞 LO2 的影响较小。值得注意的是，转移活性抑制实验表明，10n 通过抑制高转移性 SMMC-7721 细胞系中的细胞迁移和侵袭，也表现出显著的抗转移作用，并比 ADM 更能剂量依赖性地逆转 TGF-β1 诱导的上皮-间充质转化（EMT）过程。最后，10n 在体内也对 SMMC-7721 细胞系具有低急性毒性和强大的肿瘤生长抑制作用。我们的研究结果表明，新型香豆素/吡唑肟杂种是进一步研究的有前途的治疗剂候选物。
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