Binding Models of Copper(II) Thiosemicarbazone Complexes with Human Serum Albumin: A Speciation Study

May, Nóra V.; Jancsó, Attila; Enyedy, Éva A.

doi:10.3390/molecules26092711

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…Conditional stability constants for the formation of the corresponding ternary complexes (log K 1 ′ and log K 2 ′) were determined at pH 7.6 by UV–vis spectrophotometry using the wavelength range of the CT bands (Figure S21). The evaluation of the UV–vis spectra confirms the formation of two ternary complexes in both systems with 1:1:1 and 1:1:2 stoichiometries. The corresponding equilibrium constants are listed in Table and Table S7.…”

Section: Resultsmentioning

confidence: 66%

Copper(II) Complexes of Pyridine-2,6-dicarboxamide Ligands with High SOD Activity

et al. 2022

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Copper(II) complexes of pyridine-based ligands functionalized with alanine (PydiAla) and tyrosine (PydiTyr) moieties have been synthesized as novel superoxide dismutase mimics. The complexes were characterized by pH-potentiometric, spectroscopic (UV–vis, circular dichroism, mass spectrometry, electron paramagnetic resonance spectroscopy), computational (DFT), and X-ray diffraction methods. Both ligands form high stability copper(II) complexes via the (Npy,N–,N–) donor set supported by the binding of the carboxylate pendant arms. Although the coordination mode is the same for the two systems, the tyrosine containing counterpart exhibits increased copper(II) binding affinity, which is most likely due to the presence of the aromatic moiety of the side chains. Both copper(II) complexes are capable of binding N-methylimidazole, and the formation of the corresponding ternary species was observed at physiological pH. The binary and ternary copper(II) complexes exhibit high SOD activity. The PydiTyr complex exhibits about 1 order of magnitude higher activity than the PydiAla complex. This is probably due to the presence of the phenolic OH group in the former species, which promotes the binding of the superoxide anion radical to the metal center. The results serve as a basis for designing highly efficient copper(II) mimics for medical and practical applications.

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Section: Resultsmentioning

confidence: 66%

Copper(II) Complexes of Pyridine-2,6-dicarboxamide Ligands with High SOD Activity

et al. 2022

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“…In addition, the data revealed that Cu(II)-TSCs can form ternary complexes, most likely with a His on the surface of HSA. 29 , 30 Recently, the binding of Cu(II)-Triapine with pure HSA in aqueous 30% DMSO solution was also studied by Enyedy et al 38 Moreover, UV-VIS measurements with pure HSA suggest that there is also a non-covalent interaction between the metal-free TSC and binding pocket(s) of HSA.…”

Section: Discussionmentioning

confidence: 99%

Human serum albumin as a copper source for anticancer thiosemicarbazones

Schaier,

Falcone,

Prstek

et al. 2023

Metallomics

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Thiosemicarbazones (TSCs) are a class of biologically active compounds with promising anticancer activity. Their typical mechanism, especially of the clinically far developed representative Triapine, is chelation of iron (Fe), with the Fe-containing enzyme ribonucleotide reductase as primary intracellular target. However, for the subclass of terminally disubstituted, nanomolar-active derivatives like Dp44mT and Me2NNMe2, recent findings suggest that the chelation, stability, and reduction properties of the copper(II) (Cu) complexes are essential for their modes of action. Consequently, it is important to elucidate whether blood serum Cu(II) is a potential metal source for these TSCs. To gain more insights, the interaction of Triapine, Dp44mT or Me2NNMe2 with purified human serum albumin (HSA) as the main pool of labile Cu(II) was investigated by UV-vis and electron paramagnetic resonance (EPR) measurements. Subsequently, a size-exclusion chromatography inductively coupled plasma mass spectrometry (SEC-ICP-MS) method for the differentiation of Cu species in serum was developed, especially separating the non-labile Cu enzyme ceruloplasmin from HSA. The results indicate that the TSCs specifically chelate copper from the N-terminal Cu-binding site of HSA. Furthermore, the Cu(II)-TSC complexes were shown to form ternary HSA conjugates, most likely via histidine. Noteworthy, Fe-chelation from transferrin was not overserved, even not for Triapine. In summary, the labile Cu pool of HSA is a potential source for Cu-TSC complex formation and, consequently, distinctly influences the anticancer activity and pharmacological behavior of TSCs.

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“…However, the situation is different for complexes containing ligands. These have been extensively tested in phase I, II and III clinical trials for the treatment of various diseases such as Alzheimer’s and Menkes disease, and their effectiveness as antineoplastics has also been researched [ 78 , 79 , 80 , 81 , 82 , 83 ]. The most representative copper(II) complexes with antitumor potential are CasIII-Ia and CasII-gly from the family of Casiopeines ® ( Figure 2 C,D); these are now in phase I clinical trials in Mexico [ 30 ].…”

Section: Mechanisms Of Action Of Platinum(ii) and Copper(ii) Complexesmentioning

confidence: 99%

Recently Reported Biological Activities and Action Targets of Pt(II)- and Cu(II)-Based Complexes

Maciel-Flores,

Lozano-Alvarez,

Bivián-Castro

2024

Molecules

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Most diseases that affect human beings across the world are now treated with drugs of organic origin. However, some of these are associated with side effects, toxicity, and resistance phenomena. For the treatment of many illnesses, the development of new molecules with pharmacological potential is now an urgent matter. The biological activities of metal complexes have been reported to have antitumor, antimicrobial, anti-inflammatory, anti-infective and antiparasitic effects, amongst others. Metal complexes are effective because they possess unique properties. For example, the complex entity possesses the effective biological activity, then the formation of coordination bonds between the metal ions and ligands is controlled, metal ions provide it with extraordinary mechanisms of action because of characteristics such as d-orbitals, oxidation states, and specific orientations; metal complexes also exhibit good stability and good physicochemical properties such as water solubility. Platinum is a transition metal widely used in the design of drugs with antineoplastic activities; however, platinum is associated with side effects which have made it necessary to search for, and design, novel complexes based on other metals. Copper is a biometal which is found in living systems; it is now used in the design of metal complexes with biological activities that have demonstrated antitumoral, antimicrobial and anti-inflammatory effects, amongst others. In this review, we consider the open horizons of Cu(II)- and Pt(II)-based complexes, new trends in their design, their synthesis, their biological activities and their targets of action.

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Binding Models of Copper(II) Thiosemicarbazone Complexes with Human Serum Albumin: A Speciation Study

Cited by 10 publications

References 37 publications

Copper(II) Complexes of Pyridine-2,6-dicarboxamide Ligands with High SOD Activity

Copper(II) Complexes of Pyridine-2,6-dicarboxamide Ligands with High SOD Activity

Human serum albumin as a copper source for anticancer thiosemicarbazones

Recently Reported Biological Activities and Action Targets of Pt(II)- and Cu(II)-Based Complexes

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