Synthesis and antitumor mechanisms of two novel platinum(ii) complexes with 3-(2 '-benzimidazolyl)-7-methoxycoumarin
Synthesis and antitumor mechanisms of two novel platinum(ii) complexes with 3-(2 '-benzimidazolyl)-7-methoxycoumarin
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两种新型铂(ii)与3-(2'-苯并咪唑基)-7-甲氧基香豆素配合物的合成和抗肿瘤机制
DOI：
10.1039/c8mt00125a
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发表时间：
2018
期刊：
影响因子：
3.4
通讯作者：
Liang Hong
中科院分区：
文献类型：
--
作者：
Qin Qi Pin;Wang Shu Long;Tan Ming Xiong;Wang Zhen Feng;Huang Xiao Ling;Wei Qing Min;Shi Bei Bei;Zou Bi Qun;Liang Hong
以3-（2′-苯并咪唑基）-8-甲氧基香豆素（H-MeOBC）为配体，合成了两种新型铂配合物[PtCl 2（H-MeOBC）（DMSO）]（Pt 1）和[Pt 2Cl 3（MeOBC）（DMSO）2]（Pt 2），并对其抗肿瘤活性进行了研究。在所有的肿瘤细胞中，双铂（ii）配合物Pt 2表现出最强的活性，其对顺铂耐药的SK-OV-3/DDP癌细胞的IC 50值为0.5 ± 0.2 μM。在SK-OV-3/DDP细胞中，Pt 2与顺铂、H-MeOBCandPt 1相比显示出20.1-196.0倍的活性增加。Pt 1和Pt 2对正常HL-7702细胞的抑制率较低。进一步的研究表明Pt 2是一种新的与c-myc启动子元件结合的端粒酶抑制剂。机制研究表明，双铂（ii）络合物Pt 2阻滞细胞周期在G2/M期，诱导凋亡，并导致线粒体功能障碍。
Two novel platinum(ii) complexes, [PtCl2(H-MeOBC)(DMSO)] (Pt1) and [Pt2Cl3(MeOBC)(DMSO)2] (Pt2), with 3-(2′-benzimidazolyl)-8-methoxycoumarin (H-MeOBC) as the ligand were synthesized and evaluated for their antiproliferative activity. Among all the tumor cells, dual-Pt(ii) complexPt2exhibited the most potent activity, with an IC50value of 0.5 ± 0.2 μM against cisplatin-resistant SK-OV-3/DDP cancer cells. In the case of SK-OV-3/DDP cells,Pt2displayed a 20.1–196.0-fold increased activity when compared with cisplatin,H-MeOBCandPt1. Importantly,Pt1andPt2displayed low inhibitory rates against normal HL-7702 cells. Further investigation revealed thatPt2is a novel telomerase inhibitor binding to c-myc promoter elements. Mechanistic studies demonstrated that dual-Pt(ii) complexPt2arrests the cell cycle at the G2/M phase and induces apoptosis and causes mitochondrial dysfunction.