Seven new Casiopeinas® were synthesized and properly characterized. These novel compounds have a general formula [Cu(N–N)(Indo)]NO₃, where Indo is deprotonated indomethacin and N–N is either bipyridine or phenanthroline with some methyl-substituted derivatives, belonging to the third generation of Casiopeinas®. Spectroscopic characterization suggests a square-based pyramid geometry and voltammetry experiments indicate that the redox potential is strongly dependent on the N–N ligand. All the presented compounds show high cytotoxic efficiency, and most of them exhibit higher efficacy compared to the well-known cisplatin drug and acetylacetonate analogs of the first generation. Computational calculations show that antiproliferative behavior can be directly related to the volume of the molecules. Besides, a chitosan (CS)–polyacrylamide (PNIPAAm) nanogel was synthesized and characterized to examine the encapsulation and release properties of the [Cu(4,7-dimethyl-1,10-phenanthroline)(Indo)]NO₃ compound. The results show good encapsulation performance in acidic conditions and a higher kinetic drug release in acidic media than at neutral pH. This result can be described by the Peppas–Sahlin model and indicates a release mechanism predominantly by Fick diffusion.

中文翻译：

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Casiopeinas® 第三代，含吲哚美辛：合成、表征、DFT 研究、抗增殖活性和纳米封装

合成了七种新的 Casiopeinas® 并进行了适当的表征。这些新化合物具有通式 [Cu(N–N)( Indo )]NO ₃，其中Indo是去质子化的吲哚美辛，N-N 是联吡啶或菲咯啉，带有一些甲基取代的衍生物，属于第三代 Casiopeinas®。光谱表征表明基于正方形的金字塔几何形状和伏安实验表明氧化还原电位强烈依赖于 N-N 配体。所有提出的化合物都显示出很高的细胞毒效率，并且与众所周知的第一代顺铂药物和乙酰丙酮化物类似物相比，它们中的大多数都表现出更高的功效。计算计算表明，抗增殖行为与分子的体积直接相关。此外，合成了壳聚糖（CS）-聚丙烯酰胺（PNIPAAm）纳米凝胶并对其进行了表征，以检查[Cu（4,7-二甲基-1,10-菲咯啉）（Indo )]NO ₃化合物。结果表明在酸性条件下具有良好的包封性能，并且在酸性介质中比在中性 pH 条件下具有更高的动力学药物释放。该结果可以用 Peppas-Sahlin 模型来描述，并表明主要通过 Fick 扩散的释放机制。