de Medeiros Wendy M T Q, de Medeiros Mayara J C, Carvalho Edinilton M, de Lima Jailma A, da S Oliveira Verônica, de B Pontes Ana C F, da Silva Francisco O N, Ellena Javier A, de O Rocha Hugo A, de Sousa Eduardo H S, de L Pontes Daniel
Laboratório de Química de Coordenação e Polímeros (LQCPol), Instituto de Química, Universidade Federal do Rio Grande do Norte (UFRN) Natal 59078-970 Brazil
Laboratório de Bioinorgânica, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará (UFC) Cx. Postal 6021 Fortaleza 60440-900 Brazil.
RSC Adv. 2018 May 10;8(30):16873-16886. doi: 10.1039/c8ra03626h. eCollection 2018 May 3.
Vanillin (vanH) is the major component of vanilla and one of the most widely used flavoring agents. In this work the complex [Cu(phen)(van)] was prepared and characterized by structural (X-ray), spectroscopic (IR, UV-Vis, EPR) and electrochemical techniques. This compound showed an octahedral geometry with an unusual arrangement of the vanillin ligands, where the methoxy groups of the vanillinate ions are coordinated opposite to each other. The compound promoted DNA cleavage in the presence of glutathione (GSH) and HO. At 40 μmol L of complex with GSH (10 mmol L), there is a complete cleavage of DNA to nicked form II, while only at 10 μmol L of this complex with HO (1 mmol L) an extensive cleavage leading to form III took place. Additionally, we have evidences of superoxide generation upon reaction with GSH. Therefore, DNA fragmentation occurs likely through an oxidative pathway. MTT assays indicated that the complex is highly cytotoxic against three distinct cell lines: B16-F10 (IC = 3.39 ± 0.61 μmol L), HUH-7 (IC = 4.22 ± 0.31 μmol L) and 786-0 (IC = 10.38 ± 0.91 μmol L). Flow cytometry studies conducted with 786-0 cell line indicated cell death might occur by apoptosis. Cell cycle progression evaluated at 5 and 10 μmol L resulted in a clear increase of 786-0 cells at G1 phase and depletion of G2/M, while higher doses showed an expressive increase of sub-G1 phase. Altogether, these results pointed out to a promising biological activity and potential as an anti-cancer agent.
香草醛（vanH）是香草的主要成分，也是使用最为广泛的调味剂之一。在本研究中，制备了配合物[Cu(phen)(van)]，并通过结构分析（X射线）、光谱分析（红外光谱、紫外可见光谱、电子顺磁共振）和电化学技术对其进行了表征。该化合物呈现八面体几何构型，香草醛配体排列方式独特，香草酸离子的甲氧基彼此相对配位。该化合物在谷胱甘肽（GSH）和过氧化氢（HO）存在的情况下能促进DNA裂解。在40 μmol/L的配合物与GSH（10 mmol/L）存在时，DNA完全裂解为切口形式II，而仅在10 μmol/L的该配合物与HO（1 mmol/L）存在时，才会发生导致形成形式III的广泛裂解。此外，我们有证据表明与GSH反应会产生超氧阴离子。因此，DNA片段化可能通过氧化途径发生。MTT实验表明，该配合物对三种不同的细胞系具有高度细胞毒性：B16-F10（IC = 3.39 ± 0.61 μmol/L）、HUH-7（IC = 4.22 ± 0.31 μmol/L）和786-0（IC = 10.38 ± 0.91 μmol/L）。对786-0细胞系进行的流式细胞术研究表明，细胞死亡可能通过凋亡发生。在5和10 μmol/L浓度下评估细胞周期进程，结果显示786-0细胞在G1期明显增加，G2/M期减少，而更高剂量则显示亚G1期显著增加。总之，这些结果表明该配合物具有良好的生物活性和作为抗癌剂的潜力。
