Synthesis, characterization and biological activity of gallium(III) complexes with non-symmetrical N₂O-donor Schiff bases

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• 作者：Diego S. Padilha^a ; Yan F. Santos^a ; Letí ; cia C. Giacomin^a ; Frederico A.V. Castro^a ; Marcos D. Pereira^a ; Alexandre B. Rocha^a ; Jackson A.L.C. Resende^b ; ^c ; Marciela Scarpellini^a ; ^{marciela@iq.ufrj.br}
• 关键词：Gallium complexes ; Metallodrugs ; Cancer ; A-549 ; Schiff bases
• 刊名：Polyhedron
• 出版年：2017
• 出版时间：17 February 2017
• 年：2017
• 卷：123
• 期：Complete
• 页码：480-489
• 全文大小：1171 K
• 卷排序：123

文摘

Cisplatin and its analogues are some of the most widely used anticancer drugs. However, toxicity and resistance have limited their use, and gallium compounds have emerged as an alternative, due to their remarkable antitumor activity and low toxicity. In this paper, we report on four new mononuclear gallium(III) complexes with the general formula [Ga(bhi-R)2]+, where bhi-R (R = –NO2, –Br, –Cl and –OCH3) is the deprotonated form of imidazole/phenol-containing tridentate Schiff bases. The molecular structures of C1–C4 were solved by single crystal X-ray diffraction revealing mononuclear and isostructural complexes, with the metal center in distorted octahedral geometries. In all cases, the gallium(III) is coordinated to two ligand molecules arranged in meridional fashion, through the imidazole and imino nitrogen atoms, and to the phenolate oxygen. Complexes C1–C4 were also characterized in solution by spectroscopic and spectrometric techniques. DFT calculations were performed to assist the interpretation of experimental results, and also allowed to establish the reasons why only meridional isomers were obtained. The stability of all complexes was evaluated in PBS buffer (1% DMSO) over 24 h, and results indicate partial hydrolysis in this period. Finally, the biological activity of C1–C4 was evaluated on human tumor cell lines MCF-7 (breast adenocarcinoma), A-549 (lung adenocarcinoma epithelial) and PC-3 (prostate adenocarcinoma). Complex C1 was the most active, being effective and selective for A-549. The IC50 (94.12 ± 4.62) of C1 is lower than the value (135.10 ± 6.50) obtained for cisplatin, which was tested as a metallodrug reference under the same experimental conditions.