Morais Tânia S, Marques Fernanda, Madeira Paulo J Amorim, Robalo Maria Paula, Garcia Maria Helena
Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Lisboa, Portugal.
Pharmaceuticals (Basel). 2022 Jul 14;15(7):862. doi: 10.3390/ph15070862.
Ruthenium complexes are emerging as one of the most promising classes of complexes for cancer therapy. However, their limited aqueous solubility may be the major limitation to their potential clinical application. In view and to contribute to the progress of this field, eight new water-soluble Ru(II) organometallic complexes of general formula [RuCp(TPPMS)(L)] [CFSO], where TPPMS = diphenylphosphane-benzene-3-sulfonate, for = 2, L is an imidazole-based ligand (imidazole, 1-benzylimidazole, 1-butylimidazole, (1-(3-aminopropyl)imidazole), and (1-(4-methoxyphenyl)imidazole)), and for = 1, L is a bidentate heteroaromatic ligand (2-benzoylpyridine, (di(2-pyridyl)ketone), and (1,2-(2-pyridyl)benzo-[b]thiophene)) were synthesized and characterized. The new complexes were fully characterized by NMR, FT-IR, UV-vis., ESI-HRMS, and cyclic voltammetry, which confirmed all the proposed molecular structures. The antiproliferative potential of the new Ru(II) complexes was evaluated on MDAMB231 breast adenocarcinoma, A2780 ovarian carcinoma, and HT29 colorectal adenocarcinoma cell lines, showing micromolar (MDAMB231 and HT29) and submicromolar (A2780) IC values. The interaction of complex with human serum albumin (HSA) and fatty-acid-free human serum albumin (HSA) was evaluated by fluorescence spectroscopy techniques, and the results revealed that the ruthenium complex strongly quenches the intrinsic fluorescence of albumin in both cases.
钌配合物正成为癌症治疗中最有前景的配合物类别之一。然而，其有限的水溶性可能是其潜在临床应用的主要限制。鉴于此并为推动该领域的进展，合成并表征了八种通式为[RuCp(TPPMS)(L)][CFSO]的新型水溶性Ru(II)有机金属配合物，其中对于n = 2，L是基于咪唑的配体（咪唑、1-苄基咪唑、1-丁基咪唑、(1-(3-氨基丙基)咪唑)和(1-(4-甲氧基苯基)咪唑)），对于n = 1，L是双齿杂芳族配体（2-苯甲酰基吡啶、(二(2-吡啶基)酮)和(1,2-(2-吡啶基)苯并[b]噻吩)）。通过核磁共振、傅里叶变换红外光谱、紫外可见光谱、电喷雾高分辨质谱和循环伏安法对这些新型配合物进行了全面表征，证实了所有提出的分子结构。在MDAMB231乳腺腺癌、A2780卵巢癌和HT29结肠腺癌细胞系上评估了新型Ru(II)配合物的抗增殖潜力，结果显示其半数抑制浓度（IC）值在微摩尔级别（MDAMB231和HT29）和亚微摩尔级别（A2780）。通过荧光光谱技术评估了配合物与人类血清白蛋白（HSA）和无脂肪酸人类血清白蛋白（HSA）的相互作用，结果表明在这两种情况下，钌配合物均能强烈淬灭白蛋白的固有荧光。
