8-羟基喹啉-N-氧化物铜（II）和锌（II）-菲啰啉和联吡啶配合物的设计、合成、结构和抗肿瘤评价。
8-hydroxyquinoline-N-oxide copper(II)- and zinc(II)-phenanthroline and bipyridine coordination compounds: Design, synthesis, structures, and antitumor evaluation.
机构信息
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.
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.
出版信息
J Inorg Biochem. 2024 Feb;251:112443. doi: 10.1016/j.jinorgbio.2023.112443. Epub 2023 Dec 2.
Fourteen novel tumor-targeting copper(II) and zinc(II) complexes, [Cu(ONQ)(QD1)(NO)]·CHOH (NQ3), [Cu(ONQ)(QD2)(NO)] (NQ2), [Cu(NQ)(QD2)Cl] (NQ3), [Cu(ONQ)(QD1)Cl] (NQ4), Cu(ONQ)(QD3) (NQ5), [Cu(ONQ)(QD3)Cl] (NQ6), [Zn(ONQ)(QD4)Cl] (NQ7), [Zn(ONQ)(QD1)Cl] (NQ8), [Zn(ONQ)(QD5)Cl] (NQ9), [Zn(ONQ)(QD2)Cl] (NQ10), [Zn(ONQ)(QD6)Cl] (NQ11), [Zn(ONQ)(QD7)Cl] (NQ12), and [Zn(ONQ)(QD3)Cl] (NQ13) supported on 8-hydroxyquinoline-N-oxide (H-ONQ), 2,2'-dipyridyl (QD1), 5,5'-dimethyl-2,2'-bipyridyl (QD2), 1,10-phenanthroline (QD3), 4,4'-dimethoxy-2,2'-bipyridyl (QD4), 4,4'-dimethyl-2,2'-bipyridyl (QD5), 5-chloro-1,10-phenanthroline (QD6), and bathophenanthroline (QD7), were first synthesized and characterized using various spectroscopic techniques. Furthermore, NQ1-NQ13 exhibited higher antiproliferative activity and selectivity for cisplatin-resistant SK-OV-3/DDP tumor cells (CiSK3) compared to normal HL-7702 cells based on results obtained from the cell counting Kit-8 (CCK-8) assay. The complexation of copper(II) ion with QD2 and ONQ ligands resulted in an evident increase in the antiproliferation of NQ1-NQ6, with NQ6 exhibiting the highest antitumor potency against CiSK3 cells compared to NQ1-NQ5, H-ONQ, QD1-QD7, and NQ7-NQ13 as well as the reference cisplatin drug with an IC value of 0.17 ± 0.05 μM. Mechanistic studies revealed that NQ4 and NQ6 induced apoptosis of CiSK3 cells via mitophagy pathway regulation and adenosine triphosphate (ATP) depletion. Further, the differential induction of mitophagy decreased in the order of NQ6 > NQ4, which can be attributed to the major impact of the QD3 ligand with a large planar geometry and the Cl leaving group within the NQ6 complex. In summary, these results confirmed that the newly synthesized H-ONQ copper(II) and zinc(II) coordination metal compounds NQ1-NQ13 exhibit potential as anticancer drugs for cisplatin-resistant ovarian CiSK3 cancer treatment.
十四种新型肿瘤靶向铜(II)和锌(II)配合物，[Cu(ONQ)(QD1)(NO)]·CHOH (NQ3)、[Cu(ONQ)(QD2)(NO)] (NQ2)、[Cu(NQ)(QD2)Cl] (NQ3)、[Cu(ONQ)(QD1)Cl] (NQ4)、Cu(ONQ)(QD3) (NQ5)、[Cu(ONQ)(QD3)Cl] (NQ6)、[Zn(ONQ)(QD4)Cl] (NQ7)、[Zn(ONQ)(QD1)Cl] (NQ8)、[Zn(ONQ)(QD5)Cl] (NQ9)、[Zn(ONQ)(QD2)Cl] (NQ10)、[Zn(ONQ)(QD6)Cl] (NQ11)、[Zn(ONQ)(QD7)Cl] (NQ12)和[Zn(ONQ)(QD3)Cl] (NQ13)，以 8-羟基喹啉-N-氧化物 (H-ONQ)、2,2'-联吡啶 (QD1)、5,5'-二甲基-2,2'-联吡啶 (QD2)、1,10-菲咯啉 (QD3)、4,4'-二甲氧基-2,2'-联吡啶 (QD4)、4,4'-二甲基-2,2'-联吡啶 (QD5)、5-氯-1,10-菲咯啉 (QD6)和浴铜灵 (QD7)为配体，首次通过各种光谱技术进行了合成和表征。此外，基于细胞计数试剂盒-8 (CCK-8) 测定的结果，NQ1-NQ13 对顺铂耐药 SK-OV-3/DDP 肿瘤细胞 (CiSK3) 表现出更高的增殖抑制活性和选择性，而对正常 HL-7702 细胞则没有。铜(II)离子与 QD2 和 ONQ 配体的络合导致 NQ1-NQ6 的增殖抑制作用明显增强，与 NQ1-NQ5、H-ONQ、QD1-QD7 和 NQ7-NQ13 以及顺铂参考药物相比，NQ6 对 CiSK3 细胞具有最高的抗肿瘤活性，IC 值为 0.17±0.05 μM。机制研究表明，NQ4 和 NQ6 通过调节线粒体自噬途径和三磷酸腺苷 (ATP) 耗竭诱导 CiSK3 细胞凋亡。此外，线粒体自噬的差异诱导按 NQ6>NQ4 的顺序降低，这可以归因于具有大平面几何形状和 NQ6 配合物中 Cl 离去基团的 QD3 配体的主要影响。总之，这些结果证实，新合成的 H-ONQ 铜(II)和锌(II)配位金属化合物 NQ1-NQ13 作为顺铂耐药卵巢 CiSK3 癌症治疗的抗癌药物具有潜力。
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