Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 450075, Prospekt Oktyabrya 141, Ufa, Russia.
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Leninsky Prospekt 47, Moscow, Russia.
Metallomics. 2023 Jun 1;15(6). doi: 10.1093/mtomcs/mfad037.
1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-containing products to study cytotoxic properties. New mononuclear and binuclear Cu(II) complexes with 1-(N,N-dimethylamino)methyl-6-quinolinol were synthesized for the first time. The same way Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized. The structures of mono- and binuclear Cu(II) complexes with 1-aminomethyl-2-naphtol were confirmed by X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat, K562, U937, MDA-MB-231, MCF7, T47D, and HEK293 cells. The induction of apoptosis and the effect of novel Cu complexes on the cell cycle were investigated. The cells showed a higher sensitivity to mononuclear Cu(II) complex with 1-(N,N-dimethylamino)methyl-6-quinolinolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.
1-(二甲氨基)甲基-6-喹啉醇支架是抗癌药物拓扑替康分子的结构部分，被修饰成含铜产物，以研究其细胞毒性。首次合成了具有 1-(N,N-二甲氨基)甲基-6-喹啉醇的单核和双核 Cu(II)配合物。以同样的方式合成了 1-(二甲基氨基)甲基-2-萘醇配体的 Cu(II)配合物。单核和双核 Cu(II)配合物的结构通过 X 射线衍射得到证实。用 1-氨甲基-2-萘醇合成的化合物对 Jurkat、K562、U937、MDA-MB-231、MCF7、T47D 和 HEK293 细胞进行了体外细胞毒性活性检测。研究了细胞凋亡的诱导和新型 Cu 配合物对细胞周期的影响。结果表明，单核 Cu(II)配合物对 1-(N,N-二甲氨基)甲基-6-喹啉醇配体的细胞具有更高的敏感性。所有合成的 Cu(II)配合物的抗肿瘤活性均高于药物拓扑替康、喜树碱和含铂顺铂。
