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寻找对卵巢癌细胞具有细胞毒性的化合物:新型樟脑羧酸酯和樟脑羧酰胺银配合物的合成、表征及活性评价。

Search for cytotoxic compounds against ovarian cancer cells: Synthesis, characterization and assessment of the activity of new camphor carboxylate and camphor carboxamide silver complexes.

机构信息

Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.

CQFM-Centro de Química-Física Molecular, IN-Institute for Nanosciences and Nanotechnologies, IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.

出版信息

J Inorg Biochem. 2018 Nov;188:88-95. doi: 10.1016/j.jinorgbio.2018.08.011. Epub 2018 Aug 16.

DOI:10.1016/j.jinorgbio.2018.08.011
PMID:30125832
Abstract

Five silver camphor complexes of formulae [Ag(L)(L')] (1,3,5) or [Ag(L)(L')] (2,4) were synthesized from silver nitrate and the suitable camphor carboxylate (L) or camphor carboxamides (L, L). The complexes were characterized by elemental analysis and spectroscopic techniques (NMR, FTIR, XPS). Computational calculations support coordination of the carboxylate group to silver, in the case of complex 2 and combined mixed keto/carboxylate in the case of complex 1. The stability of the complexes highly relies on the tetrahedral geometry of the lithium ion that binds to four oxygen atoms of the camphor carboxylate ligands. The redox properties of complexes 1 and 4 studied by cyclic voltammetry confirm the facile reduction of the metal sites that depending on the experimental conditions may lead to formation of silver nanoparticles as confirmed by XPS and TEM. Complexes 1, 2 and 4 were tested for cytotoxic activities against A2780 (IC, 11-14 μM) and A2780 cisplatin resistant (A2780cisR) (IC, 4-7 μM) cells using the MTT assay. The result showed that the complexes have anticancer activity higher than cisplatin. Complex 1 was also probed for cytotoxicity against the non-tumoral human embryonic kidney (HEK 293, IC, 62.2 ± 16 μM) cells showing low toxicity in agreement with the silver camphor carboxylate complexes having a considerable selectivity for the ovarian cancer cells A2780 and cisplatin resistant A2780cisR which is a key point under pharmacological uses.

摘要

五个银樟脑配合物的配方[Ag(L)(L')](1,3,5)或[Ag(L)(L')](2,4)是由硝酸银和合适的樟脑羧酸(L)或樟脑酰胺(L,L')合成的。这些配合物通过元素分析和光谱技术(NMR、FTIR、XPS)进行了表征。计算计算支持羧酸根与银的配位,在 2 号配合物的情况下为配合物,在 1 号配合物的情况下为混合酮/羧酸根。配合物的稳定性高度依赖于与樟脑羧酸配体的四个氧原子结合的锂离子的四面体几何形状。通过循环伏安法研究配合物 1 和 4 的氧化还原性质证实了金属位点的易还原,根据实验条件,这可能导致银纳米粒子的形成,这一点通过 XPS 和 TEM 得到了证实。用 MTT 法测定了配合物 1、2 和 4 对 A2780(IC,11-14μM)和 A2780 顺铂耐药(A2780cisR)(IC,4-7μM)细胞的细胞毒性活性。结果表明,配合物具有比顺铂更高的抗癌活性。配合物 1 也被用于对非肿瘤性人胚肾(HEK 293,IC,62.2±16μM)细胞的细胞毒性进行探测,显示出低毒性,与樟脑银羧酸配合物对卵巢癌细胞 A2780 和顺铂耐药 A2780cisR 具有相当的选择性一致,这是药理学应用的一个关键点。

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