Synthesis and characterization of tannic acid–copper complex: A promising anticholinesterase drug

• Published in: Polyhedron 2024-12, Vol.264, p.117213, Article 117213
• Main Authors: Ferreira, Thaís Araújo Gomes, Campelo, Matheus da Silva, Alves, Daniela Ribeiro, da Silva, Wildson Max Barbosa, de Morais, Selene Maia, Krambrock, Klaus, Ricardo, Nágila Maria Pontes Silva, de Menezes, Jane Eire Silva Alencar, da Silva, Francisco Luan Fonsêca, Pinheiro, Solange de Oliveira, Ribeiro, Maria Elenir Nobre Pinho
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase enzyme; Antioxidant; Copper (II) ion; Inorganic complexes; Tannic acid
• ISSN: 0277-5387
• DOI: 10.1016/j.poly.2024.117213

[Display omitted] This study aimed to present an optimized synthetic pathway for a complex formed between copper (II) metal ion and tannic acid (TA), which have a variety of pharmacological properties. The study also focused on characterizing this metallodrug, carrying out in vitro antioxidant and acetylcholinesterase enzyme (AChE) inhibition assays, and performing in vivo toxicity assay against zebrafish (Danio rerio), thus expanding the area of study involving syntheses of metal complexes to act as therapeutic agents. Through various characterization techniques, including UV–Vis Absorption Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Thermal Analysis (TG and DTG), 1H Nuclear Magnetic Resonance (1H NMR), Inductively Coupled Plasma with Optical Emission Spectrometry (ICP-OES), and Electron Paramagnetic Resonance (EPR), it was confirmed that the metal ion is coordinated to the ligand, exhibiting distorted planar square geometry with mononuclear copper (3.10 ± 0.10 % copper by ICP-OES). In vitro tests demonstrated that the TA–Cu complex presents antioxidant activity against DPPH (IC50 = 2.26 ± 0.01 µg mL−1) and ABTS (IC50 = 1.91 ± 0.07 µg mL−1) radical scavenging assays. These results were more promising than those obtained for the TA (4.25 ± 0.03 µg mL−1 and 3.37 ± 0.03 µg mL−1, respectively). In the in vitro inhibition of AChE assay, the TA–Cu complex (4.07 ± 0.04 µg mL−1) presented a lower IC50 value than TA (5.80 ± 0.09 µg mL−1), indicating that coordination to the metal center Cu (II) was able to improve the anticholinesterase activity of the free ligand. Furthermore, the TA–Cu complex did not show toxicity in the in vivo test with adult zebrafish for 96 h at the tested doses of 4–40 mg kg−1, with LD50 >40 mg kg−1. Thus, it is estimated that the TA–Cu complex is a metallodrug with anticholinesterase potential, representing a promising strategy for conducting future pre-clinical studies in models of Alzheimer’s disease.