Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Chemical Engineering Department, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, R. Conselheiro Emídio Navarro, 1, 1959-007 Lisboa, Portugal.
J Inorg Biochem. 2019 Nov;200:110811. doi: 10.1016/j.jinorgbio.2019.110811. Epub 2019 Aug 27.
The syntheses of the heterometallic sodium and potassium-dioxidovanadium 2D polymers, NaVO(1κNOO';2κO"-L)(HO) and KVO(1κNOO';2κO';3κO"-L)(EtOH) (where the κ notation indicates the coordinating atoms of the polydentate ligand L) derived from (3,5-di-tert-butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (HL) are reported. The polymers were characterized by IR, NMR, elemental analysis and single crystal X-ray diffraction analysis. The antiproliferative potential of 1 and 2 was examined towards four human cancer cell lines (ovarian carcinoma, A2780, colorectal carcinoma, HCT116, prostate carcinoma, PC3 and breast adenocarcinoma, MCF-7cell lines) and normal human fibroblasts. Complex 1 and 2 showed the highest cytotoxic activity against A2780 cell line (IC 8.2 and 11.3 μM, respectively) with 1 > 2 and an IC in the same range as cisplatin (IC 3.4 μM; obtained in the same experimental conditions) but, interestingly, with no cytotoxicity to healthy human fibroblasts for concentrations up to 75 μM. This high cytotoxicity of 1 in ovarian cancer cells and its low cytotoxicity in healthy cells demonstrates its potential for further biological studies. Our results suggest that both complexes induce ovarian carcinoma cell death via apoptosis and autophagy, but autophagy is the main biological cause of the reduction of viability observed and that ROS (reactive oxygen species) may play an important role in triggering cell death.
报道了杂金属钠和钾-二氧代钒二维聚合物NaVO(1κNOO';2κO"-L)(HO)和KVO(1κNOO';2κO';3κO"-L)(EtOH)的合成，其中κ符号表示多齿配体 L 的配位原子。聚合物通过 IR、NMR、元素分析和单晶 X 射线衍射分析进行了表征。研究了 1 和 2 对四种人类癌细胞系（卵巢癌 A2780、结直肠癌 HCT116、前列腺癌 PC3 和乳腺癌 MCF-7 细胞系）和正常人类成纤维细胞的抗增殖潜力。复合物 1 和 2 对 A2780 细胞系表现出最高的细胞毒性活性（IC 8.2 和 11.3 μM，分别），1>2，与顺铂（IC 3.4 μM；在相同的实验条件下获得）的 IC 相同，但有趣的是，对于浓度高达 75 μM 的健康人成纤维细胞没有细胞毒性。1 在卵巢癌细胞中的这种高细胞毒性及其在健康细胞中的低细胞毒性表明其具有进一步生物学研究的潜力。我们的结果表明，两种复合物均通过细胞凋亡和自噬诱导卵巢癌细胞死亡，但自噬是观察到的活力降低的主要生物学原因，ROS（活性氧）可能在触发细胞死亡中发挥重要作用。
