基于吖啶和其抗肿瘤活性的结构简单的菲啶类似物。

Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities.

机构信息

Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, Guangxi, China.

College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541006, Guangxi, China.

出版信息

Molecules. 2019 Jan 26;24(3):437. doi: 10.3390/molecules24030437.

DOI:10.3390/molecules24030437

PMID:30691109

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6385102/

Abstract

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds , , and , with IC values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound and compound with IC values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC value of 1.13 μM.

摘要

为了寻找有效的抗癌药物，我们设计并合成了一系列基于小檗碱的新型结构简单的类似物。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法体外检测这些类似物对人癌细胞系(HepG2、A549、NCI-H460 和 CNE1)的抗肿瘤活性。结果表明，其中一些具有良好的抗癌活性，特别是在 C-6 位带有[(二甲基氨基)乙基]氨基侧链的衍生物。平面共轭化合物、、对 CNE1 细胞的 IC 值分别为 1.20 μM、1.87 μM 和 1.19 μM，活性均强于氯化小檗碱。化合物对 HepG2 细胞和 A549 细胞的 IC 值分别为 1.19 μM 和 1.37 μM，化合物对 HepG2 细胞和 A549 细胞的活性优于小檗碱。此外，具有菲啶酮核心的化合物对所有测试细胞均表现出非凡的细胞毒性，对 CNE1 细胞的 IC 值为 1.13 μM。