Therapeutic Potential of a Water-Soluble Silver-Diclofenac Coordination Polymer on 3D Pancreatic Cancer Spheroids

• Published in: Journal of medicinal chemistry 2022-08, Vol.65 (16), p.11100-11110
• Main Authors: Jaros, Sabina W., Komarnicka, Urszula K., Kyzioł, Agnieszka, Pucelik, Barbara, Nesterov, Dmytro S., Kirillov, Alexander M., Smoleński, Piotr
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Diclofenac - pharmacology; Humans; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Polymers - chemistry; Silver - chemistry; Silver - pharmacology; Water - chemistry
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.2c00535

This work describes the traditional wet and green synthetic approaches, structural features, and extensive bioactivity study for a new coordination polymer [Ag­(μ-PTA)­(Df)­(H2O)] n ·3nH2O (1) 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 1 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 1. The obtained experimental data indicate that 1 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.