Scalese Gonzalo, Mosquillo M Florencia, Rostán Santiago, Castiglioni Jorge, Alho Irina, Pérez Leticia, Correia Isabel, Marques Fernanda, Costa Pessoa João, Gambino Dinorah
Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay.
Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
J Inorg Biochem. 2017 Oct;175:154-166. doi: 10.1016/j.jinorgbio.2017.07.014. Epub 2017 Jul 18.
In Latin America Chagas disease is an endemic illness caused by the parasite Trypanosoma cruzi (T. cruzi), killing more people than any other parasitic disease. Current chemotherapies are old and inadequate, thus the development of efficient ones is urgently needed. Vanadium-based complexes have been shown to be a promising approach both against parasitic diseases and cancer and this study aims to achieve significant advances in the pursue of effective compounds. Heteroleptic vanadium complexes of Schiff bases and polypyridine compounds were prepared and their stability in solution evaluated by EPR (Electronic Paramagnetic Resonance) and NMR spectroscopy. Their in vitro activities were evaluated against T. cruzi and a set of cells lines representative of human cancer conditions, namely ovarian, breast and prostate cancer. In T. cruzi, most of the complexes depicted IC values in the low μM range, induced changes of mitochondrial membrane potential and apoptosis. In cancer cells, complexes showed good to moderate activity and in metastatic cells (prostate PC3), some complexes inhibited the migratory ability, this suggesting that they display antimetastatic potential. Interestingly, complex 5 seemed to have a dual effect being the most cytotoxic complex on all cancer cells and also the most active anti-T-cruzi compound of the series. Globally the complexes showed promising anticancer and anti T. cruzi activities and also displayed some characteristics indicating they are worth to be further explored as antimetastatic drugs.
在拉丁美洲，恰加斯病是一种由克氏锥虫寄生虫引起的地方性疾病，其致死人数超过任何其他寄生虫病。目前的化疗方法陈旧且效果不佳，因此迫切需要开发有效的化疗方法。钒基配合物已被证明是对抗寄生虫病和癌症的一种有前景的方法，本研究旨在在寻求有效化合物方面取得重大进展。制备了席夫碱和聚吡啶化合物的杂配体钒配合物，并通过电子顺磁共振（EPR）和核磁共振光谱对其在溶液中的稳定性进行了评估。评估了它们对克氏锥虫和一组代表人类癌症情况的细胞系（即卵巢癌、乳腺癌和前列腺癌）的体外活性。在克氏锥虫中，大多数配合物的半数抑制浓度（IC）值在低微摩尔范围内，可诱导线粒体膜电位变化和细胞凋亡。在癌细胞中，配合物表现出良好至中等的活性，在转移性细胞（前列腺癌PC3细胞）中，一些配合物抑制了迁移能力。这表明它们具有抗转移潜力。有趣的是，配合物5似乎具有双重作用，它是所有癌细胞中细胞毒性最大的配合物，也是该系列中抗克氏锥虫活性最强的化合物。总体而言，这些配合物显示出有前景的抗癌和抗克氏锥虫活性，并且还表现出一些特征，表明它们作为抗转移药物值得进一步探索。
