Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin, 537000, PR China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin, 541004, PR China.
Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin, 537000, PR China.
Eur J Med Chem. 2019 Dec 15;184:111751. doi: 10.1016/j.ejmech.2019.111751. Epub 2019 Oct 2.
A series of novel organoplatinum(II) complexes, [Pt(QC1)(H-QC1)Cl] (Pt1), [Pt(QC2)(H-QC2)Cl] (Pt2), [Pt(QC3)(H-QC3)Cl] (Pt3), [Pt(QC4)(H-QC4)Cl]⋅CHOH (Pt4), [Pt(QC5)(H-QC5)Cl] (Pt5), [Pt(H-QC6)(DMSO)Cl] (Pt6), [Pt(H-QC7)(DMSO)Cl]⋅HO (Pt7), [Pt(H-QC8)(DMSO)Cl] (Pt8), [Pt(H-QC9)(DMSO)Cl]⋅CHOH (Pt9), [Pt(H-QC10)(DMSO)Cl] (Pt10) and [Pt(H-QC11)(DMSO)Cl] (Pt11), bearing quinoline-coumarin derivatives (H-QC1-H-QC11) have been first designed. Complexes Pt1-Pt11 selectively displayed obvious cytotoxicities in comparison to cisplatin for A549/DDP (cisplatin-resistant human lung adenocarcinoma) cells and HeLa cervical carcinoma cells, with IC values as low as 100 nM-10.33 μM. In addition, Pt4 and Pt5 display a green-colored luminescent properties, targeted mitochondrial membrane and, thereby induced mainly mitochondria-mediated cell apoptosis was in the following order: Pt4 > Pt5. The different anti-cancer activity of quinoline-coumarin complexes Pt4 (100 nM) and Pt5 (250 nM) were correlate with the presence of 3-(2'-quinolyl)-6-hydroxy-coumarin (H-QC4) ligand. The quinoline-coumarin complex Pt4 (2.0 mg/kg per 2 days) also displayed potent in vivo anti-tumor effect after 21 days-treated. In contrast, the H-QC4 ligand highly enhances the anti-tumor activity and selectivity of organoplatinum(II) complexes in comparison to other previously reported coumarin derivatives metal complexes.
一系列新型有机铂(II)配合物，[Pt(QC1)(H-QC1)Cl]（Pt1）、[Pt(QC2)(H-QC2)Cl]（Pt2）、[Pt(QC3)(H-QC3)Cl]（Pt3）、[Pt(QC4)(H-QC4)Cl]·CHOH（Pt4）、[Pt(QC5)(H-QC5)Cl]（Pt5）、[Pt(H-QC6)(DMSO)Cl]（Pt6）、[Pt(H-QC7)(DMSO)Cl]·HO（Pt7）、[Pt(H-QC8)(DMSO)Cl]（Pt8）、[Pt(H-QC9)(DMSO)Cl]·CHOH（Pt9）、[Pt(H-QC10)(DMSO)Cl]（Pt10）和[Pt(H-QC11)(DMSO)Cl]（Pt11），被设计成含有喹啉-香豆素衍生物（H-QC1-H-QC11）。与顺铂相比，配合物 Pt1-Pt11 对 A549/DDP（耐顺铂人肺腺癌）细胞和 HeLa 宫颈癌细胞具有明显的细胞毒性，IC 值低至 100 nM-10.33 μM。此外，Pt4 和 Pt5 显示出绿色发光性质，靶向线粒体膜，并因此主要诱导线粒体介导的细胞凋亡，顺序为：Pt4>Pt5。不同的喹啉-香豆素配合物 Pt4（100 nM）和 Pt5（250 nM）的抗癌活性与 3-（2'-喹啉基）-6-羟基香豆素（H-QC4）配体的存在有关。喹啉-香豆素配合物 Pt4（2.0 mg/kg，每 2 天一次）在 21 天治疗后也显示出很强的体内抗肿瘤作用。相比之下，与其他先前报道的香豆素衍生物金属配合物相比，H-QC4 配体显著提高了有机铂(II)配合物的抗肿瘤活性和选择性。
