JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2021-02-19 , DOI: 10.1007/s00775-021-01857-9 Sutthida Wongsuwan 1 , Jaruwan Chatwichien 2 , Bussaba Pinchaipat 3 , Sarawut Kumphune 4, 5 , David J Harding 6 , Phimphaka Harding 6 , Jaursup Boonmak 7 , Sujittra Youngme 7 , Ratanon Chotima 3
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A series of Fe(II) complexes (1–4) and Fe(III) complexes (5–8) from Fe(II)/(III) chloride and N-(8-quinolyl)-X-salicylaldimine Schiff base ligands (Hqsal-X2/X: X = Br, Cl) were successfully synthesized and characterized by spectroscopic (FT-IR, 1H-NMR), mass spectrometry, thermogravimetric analysis (TGA), and single crystal X-ray crystallographic techniques. The interaction of complexes 1–8 with calf thymus DNA (CT-DNA) was determined by UV–Vis and fluorescence spectroscopy. The complexes exhibited good DNA-binding activity via intercalation. The molecular docking between a selected complex and DNA was also investigated. The in vitro anticancer activity of the Schiff base ligands and their complexes were screened against the A549 human lung adenocarcinoma cell line. The complexes showed anticancer activity toward A549 cancer cells while the free ligands and iron chloride salts showed no inhibitory effects at 100 µM. In this series, complex [Fe(qsal-Cl2)2]Cl 6 showed the highest anticancer activity aginst A549 cells (IC50 = 10 µM). This is better than two well-known anticancer agents (Etoposide and Cisplatin). Furthermore, the possible mechanism for complexes 1–8 penetrating A549 cells through intracellular ROS generation was investigated. The complexes containing dihalogen substituents 1, 2, 5, and 6 can increase ROS in A549 cells, leading to DNA or macromolecular damage and cell-death induction.
Graphic abstract
中文翻译：
含 N-(8-喹啉基)水杨醛亚胺席夫碱配体的 Fe(II) 和 Fe(III) 配合物的合成、表征及其抗癌活性
由 Fe(II)/(III) 氯化物和N -(8-喹啉基)-X-水杨醛亚胺席夫碱配体 (成功合成了Hqsal-X 2 /X: X = Br, Cl)，并通过光谱（FT-IR、 1 H-NMR）、质谱、热重分析（TGA）和单晶X射线晶体学技术对其进行了表征。通过 UV-Vis 和荧光光谱测定复合物1-8与小牛胸腺 DNA (CT-DNA) 的相互作用。该复合物通过嵌入表现出良好的 DNA 结合活性。还研究了选定复合物与 DNA 之间的分子对接。筛选希夫碱配体及其复合物针对 A549 人肺腺癌细胞系的体外抗癌活性。该复合物对 A549 癌细胞表现出抗癌活性，而游离配体和氯化铁盐在 100 µM 时没有表现出抑制作用。在该系列中，复合物[Fe(qsal-Cl 2 ) 2 ]Cl 6对A549细胞表现出最高的抗癌活性(IC 50 = 10 µM)。这比两种著名的抗癌药物（依托泊苷和顺铂）更好。此外，还研究了复合物1 – 8通过细胞内 ROS 生成渗透 A549 细胞的可能机制。含有二卤素取代基1、2、5和6的配合物可以增加A549细胞中的ROS，导致DNA或大分子损伤和细胞死亡诱导。
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