Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix

Abstract

Every year, more Cu(II) complexes are proven to be biologically active species, but very few are developed as drugs or entered in clinical trials. This is due to their poor water solubility and lipophilicity, low stability as well as in vivo inactivation. The possibility to improve their pharmacological and/or oral administration profile by incorporation into inorganic or organic matrix was studied. Most of them are either physically encapsulated or conjugated to the matrix via a moiety able to coordinate Cu(II). As a result, a large variety of species were developed as delivery carriers. The organic carriers include liposomes, synthetic or natural polymers or dendrimers, while the inorganic ones are based on carbon nanotubes, hydrotalcite and silica. Some hybrid organic-inorganic materials based on alginate-carbonate, gold-PEG and magnetic mesoporous silica-Schiff base were also developed for this purpose.

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

“…As a result, there is a continuous search for new antitumor drugs with reduced side effects and lower toxicity. The Cu(II) systems represent beneficial species from this point of view, considering their reduced systemic toxicity [16]. Thus, several Cu(II) complexes were studied and proved to be as effective for melanoma treatment [18,29,[35][36][37][38][39][40][41][42][43]-some having, in addition, low toxicity on normal cells [18,29,[39][40][41][42][43].…”

“…Considering its biological potency, the tp scaffold is often used to develop biologically active complexes, with a net preference for Cu(II) against other metal ions. Copper(II) exhibits particular traits, such as borderline acid characteristics or stereochemical and oxidation state versatility [16]. Moreover, most of the Cu(II) complexes with tps were reported as having antiparasitic [17], antitumor, or antimicrobial activity [18].…”

Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands

“…The organic cytostatics used for melanoma chemotherapy generate severe side effects, including an increased risk of infection as well as resistance development. Hence, in a continuous search for new antitumor drugs with reduced side effects and lower toxicity, the Cu(II) complexes are preferred, considering their reduced systemic toxicity [ 18 ]. Thus, several Cu(II) species were developed as non-toxic compounds for healthy tissue but with high activity in melanoma cells [ 33 , 39 , 40 ].…”

“…Studies concerning the complexes with such ions evidenced differences concerning their mechanisms of action. Thus, while Cu(II) manifests both redox [ 18 ] and hydrolytic [ 19 ] abilities in a biological environment, Zn(II) is primarily involved in promoting the hydrolytic reactions as a result of its strong Lewis-acid character [ 5 ]. Moreover, the interaction with biomolecules can be assisted by ligands that can control both the complex stability and their interaction with aromatic components of DNA and proteins through intercalation and/or weak interactions such as dipole–dipole, electrostatic, hydrogen bonds, or π–π stacking.…”

Evaluation of the Safety and Toxicity of the Original Copper Nanocomposite Based on Poly-N-vinylimidazole

“…The application fields of such nanocomposites having a wide range of unique properties are quite diverse and include effective biomedical materials, inexpensive catalytic systems, optical nanosensors, and ecological biosorbents developing. Nevertheless, the usage of new copper-containing nanocomposites as an alternative to organic copper compounds in pharmacology and medicine is most promising [ 20 ]. Thus, it was shown that copper nanoparticles (CuNPs and CuO NPs) can be applied as antimicrobial, antifungal, anticancer, and anti-inflammatory agents as well as therapeutic agents for wound healing [ 8 , 21 ].…”