Journal
METALLOMICS
Volume 15, Issue 6, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/mtomcs/mfad037
Keywords
Cu-Complexes; Anti-Cancer Activity; Apoptosis; Cell Cycle; X-Ray
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In this study, the 1-(dimethylamino)methyl-6-quinolinol scaffold of topotecan, an anticancer drug, was modified to form copper-containing compounds for investigation of their cytotoxic properties. Mononuclear and binuclear Cu(II) complexes with 1-(N,N-dimethylamino)methyl-6-quinolinol and Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized and their structures confirmed. The compounds were tested for in vitro cytotoxic activity against various cancer cells, and the induction of apoptosis and effect on cell cycle were investigated. Mononuclear Cu(II) complex with 1-(N,N-dimethylamino)methyl-6-quinolinol ligand showed higher sensitivity, and all synthesized Cu(II) complexes exhibited higher antitumor activity compared to topotecan, camptothecin, and cisplatin.
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.
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