Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland.
Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland.
J Med Chem. 2022 Aug 25;65(16):11100-11110. doi: 10.1021/acs.jmedchem.2c00535. Epub 2022 Aug 15.
This work describes the traditional wet and green synthetic approaches, structural features, and extensive bioactivity study for a new coordination polymer [Ag(-PTA)(Df)(HO)]·3HO () that bears a silver(I) center, a 1,3,5-triaza-phosphaadamantane (PTA) linker, and a nonsteroidal anti-inflammatory drug, diclofenac (Df). Compared to cisplatin, compound exhibits both anti-inflammatory properties and very remarkable cytotoxicity toward various cancer cell lines with a high value of selectivity index. Additionally, the 3D model representing human pancreas/duct carcinoma (PANC-1) and human lung adenocarcinoma (A549) was designed and applied as a clear proof of the remarkable therapeutic potential of . The obtained experimental data indicate that induces an apoptotic pathway via reactive oxygen species generation, targeting mitochondria due to their membrane depolarization. This study broadens a group of bioactive metal-organic networks and highlights the significant potential of such compounds in developing advanced therapeutic solutions.
这项工作描述了一种新的配位聚合物 [Ag(-PTA)(Df)(HO)]·3HO () 的传统湿合成和绿色合成方法、结构特征以及广泛的生物活性研究，该聚合物具有银（I）中心、1,3,5-三氮杂环戊二烯（PTA）连接体和一种非甾体抗炎药双氯芬酸（Df）。与顺铂相比，化合物 具有抗炎特性和对各种癌细胞系的非常显著的细胞毒性，其选择性指数很高。此外，还设计并应用了代表人类胰腺/胆管癌（PANC-1）和人类肺腺癌（A549）的 3D 模型，作为 的显著治疗潜力的明确证明。获得的实验数据表明， 通过生成活性氧物种，靶向由于膜去极化而导致线粒体功能障碍的细胞，诱导细胞凋亡途径。这项研究拓宽了一组具有生物活性的金属有机网络，并强调了此类化合物在开发先进治疗解决方案方面的巨大潜力。
