Costa Joana P, Pinheiro Teresa, Martins Maria S, Carvalho M Fernanda N N, Feliciano Joana R, Leitão Jorge H, Silva Rafaela A L, Guerreiro Joana F, Alves Luís M C, Custódio Inês, Cruz João, Marques Fernanda
Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal.
IBB-Instituto de Bioengenharia e Biociências, Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal.
Antibiotics (Basel). 2022 Jul 27;11(8):1010. doi: 10.3390/antibiotics11081010.
The cytotoxic activity of four sets of camphorimine complexes based on the Cu(I), Cu(II), Ag(I), and Au(I) metal sites were assessed against the cisplatin-sensitive A2780 and OVCAR3 ovarian cancer cells. The results showed that the gold complexes were ca. one order of magnitude more active than the silver complexes, which in turn were ca. one order of magnitude more active than the copper complexes. An important finding was that the cytotoxic activity of the Ag(I) and Au(I) camphorimine complexes was higher than that of cisplatin. Another relevant aspect was that the camphorimine complexes did not interact significantly with DNA, in contrast with cisplatin. The cytotoxic activity of the camphorimine complexes displayed a direct relationship with the cellular uptake by OVCAR3 cells, as ascertained by PIXE (particle-induced X-ray emission). The levels of ROS (reactive oxygen species) formation exhibited an inverse relationship with the reduction potentials for the complexes with the same metal, as assessed by cyclic voltammetry. In order to gain insight into the toxicity of the complexes, their cytotoxicity toward nontumoral cells (HDF and V79 fibroblasts) was evaluated. The in vivo cytotoxicity of complex using the nematode was also assessed. The silver camphorimine complexes displayed the highest selectivity coefficients (activity vs. toxicity).
评估了基于铜（I）、铜（II）、银（I）和金（I）金属位点的四组樟脑亚胺配合物对顺铂敏感的A2780和OVCAR3卵巢癌细胞的细胞毒性活性。结果表明，金配合物的活性比银配合物高约一个数量级，而银配合物的活性又比铜配合物高约一个数量级。一个重要发现是，银（I）和金（I）樟脑亚胺配合物的细胞毒性活性高于顺铂。另一个相关方面是，与顺铂不同，樟脑亚胺配合物与DNA没有显著相互作用。通过PIXE（粒子诱导X射线发射）确定，樟脑亚胺配合物的细胞毒性活性与OVCAR3细胞的细胞摄取呈直接关系。通过循环伏安法评估，对于具有相同金属的配合物，活性氧（ROS）形成水平与还原电位呈反比关系。为了深入了解配合物的毒性，评估了它们对非肿瘤细胞（HDF和V79成纤维细胞）的细胞毒性。还评估了使用线虫对配合物的体内细胞毒性。银樟脑亚胺配合物表现出最高的选择性系数（活性与毒性）。
