CEQUINOR (UNLP, CCT-CONICET La Plata, asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Blvd. 120 N° 1465, La Plata 1900, Argentina.
Centro de Ciências e Tecnologias Nucleares and Departamento de Ciências e Engenharia Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal; Centro de Química Estrutural, Institute of Molecular Sciences, and Departamento de Engenharia Química, Instituto Superior Técnico, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal.
J Inorg Biochem. 2022 Nov;236:111961. doi: 10.1016/j.jinorgbio.2022.111961. Epub 2022 Aug 13.
Due to the growing prevalence of cancer diseases, new therapeutic options are urgently needed, and drugs based on metal ions other than platinum are alternatives with exciting possibilities. We report the synthesis, characterization and biological effect of mixed-ligand Fe(III)-aminophenolate complexes derived from salicylaldehyde and L-tryptophan with quinoline derivatives as co-ligands, namely 8-hydroxyquinoline (8HQ), [Fe(L)(8HQ)(HO)] (1) and its 5-cloro derivative (Cl8HQ), [Fe(L)(Cl8HQ)(HO)] (2). The complex bearing the aminophenolate and lacking the quinoline co-ligand, [Fe(L)(Cl)(HO)] (3), was prepared for comparison. The analytical and spectroscopic characterization revealed that 1 and 2 are octahedral Fe(III) complexes with the aminophenolate acting as a dianionic tridentate ligand and 8HQ co-ligands as bidentate chelates. Spectroscopic techniques and molecular docking studies were used to evaluate the ability of these complexes to bind bovine serum albumin (BSA) and calf thymus DNA. Complex 2 [Fe(L)(Cl8HQ)(HO)] was the one showing higher affinity for both biomolecules. Cell viability was assessed in breast, colorectal and bone human cancer cell lines. 1 and 2 were found to be more active than cisplatin in all cell lines tested. A non-tumoral fibroblast line (L929, mouse non-tumoral fibroblasts) was used to evaluate selectivity. The results evidence that 2 shows much higher selectivity than 1 in all cell lines tested, but particularly in bone cancer cells in which selectivity index (SI) values are 8.0 and 18.8 for 1 and 2, respectively.
由于癌症疾病的患病率不断上升，迫切需要新的治疗选择，而基于非铂金属离子的药物是具有令人兴奋的可能性的替代品。我们报告了源自水杨醛和 L-色氨酸的混合配体 Fe(III)-氨基苯酚配合物的合成、表征和生物学效应，带有喹啉衍生物作为共配体，即 8-羟基喹啉（8HQ）、[Fe(L)(8HQ)(HO)]（1）及其 5-氯衍生物（Cl8HQ）、[Fe(L)(Cl8HQ)(HO)]（2）。为了进行比较，还制备了缺乏喹啉共配体的仅含氨基苯酚配体的配合物[Fe(L)(Cl)(HO)]（3）。分析和光谱表征表明，1 和 2 是具有八面体结构的 Fe(III)配合物，其中氨基苯酚作为二阴离子三齿配体，8HQ 共配体作为双齿螯合物。光谱技术和分子对接研究用于评估这些配合物与牛血清白蛋白（BSA）和小牛胸腺 DNA 结合的能力。配合物 2 [Fe(L)(Cl8HQ)(HO)]对这两种生物分子的亲和力最高。在乳腺癌、结直肠癌和骨人癌细胞系中评估细胞活力。1 和 2 在所有测试的细胞系中均比顺铂更具活性。使用非肿瘤成纤维细胞系（L929，小鼠非肿瘤成纤维细胞）来评估选择性。结果表明，在所有测试的细胞系中，2 比 1 具有更高的选择性，但在骨癌细胞中尤其如此，1 和 2 的选择性指数（SI）值分别为 8.0 和 18.8。
