Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells

Pitucha, Monika; Korga-Plewko, Agnieszka; Czylkowska, Agnieszka; Rogalewicz, Bartłomiej; Drozd, Monika; Iwan, Magdalena; Kubik, Joanna; Humeniuk, Ewelina; Adamczuk, Grzegorz; Karczmarzyk, Zbigniew; Fornal, Emilia; Wysocki, Waldemar; Bartnik, Paulina

doi:10.3390/ijms22063104

Cited by 30 publications

(23 citation statements)

References 43 publications

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“…In addition to peptides, many types of molecules can be coordinated with Cu(II) ions. This group includes thiosemicarbazone derivatives [ 28 ], catechol-containing Schiff bases [ 29 ], or substituted benzoic acids [ 30 ]. Many of the listed derivatives have anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Kotynia

Wiatrak

Kamysz

et al. 2021

IJMS

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Antimicrobial peptides are a promising group of compounds used for the treatment of infections. In some cases, metal ions are essential to activate these molecules. Examples of metalloantibiotics are, for instance, bleomycin and dermcidin. This study is focused on three new pseudopeptides with potential biological activity. The coordination behavior of all ligands with Cu(II) and Ni(II) ions has been examined. Various analytical methods such as potentiometric titration, UV-Vis and CD spectroscopies, and mass spectrometry were used. All compounds are convenient chelators for metal ion-binding. Two of the ligands tested have histidine residues. Surprisingly, imidazole nitrogen is not involved in the coordination of the metal ion. The N-terminal amino group, Dab side chains, and amide nitrogen atoms of the peptide bonds coordinated Cu(II) and Ni(II) in all the complexes formed. The cytotoxicity of three pseudopeptides and their complexes was evaluated. Moreover, their other model allowed for assessing the attenuation of LPS-induced cytotoxicity and anti-inflammatory activities were also evaluated, the results of which revealed to be very promising.

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Section: Introductionmentioning

confidence: 99%

Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Kotynia

Wiatrak

Kamysz

et al. 2021

IJMS

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“…It has also been shown that complex formation with copper leads to an increase in the selectivity of the TSCs against melanoma cells. For example, complexes of triapine with copper exhibit greater cytotoxicity in relation to tumor cells and less in relation to normal cells than the free ligand [226][227][228][229][230][231]. Copper accumulates in tumor cells due to the It has also been shown that complex formation with copper leads to an increase in the selectivity of the TSCs against melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine

Timoshnikov

Selyutina

Polyakov

et al. 2022

IJMS

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The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones) e.g., deferiprone, anthraquinones e.g.,doxorubicin and thiosemicarbazones e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential clinical applications, including anticancer activity. Furthermore, the redox properties of these three classes of chelators were compared to those of the iron chelating drugs and also to vitamin C, with an emphasis on their potential clinical interactions and future clinical application prospects in cancer, neurodegenerative and other diseases.

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“…Several anti-cancer mechanisms of action have been proposed for the new connections; for example, the destruction of the tyrosyl radical, inhibition of synthesized DNA, inhibition of Topo I/II α, and mobilization of intracellular Fe [ 5 ]. Additionally, complexes of thiosemicarbazones with Cu (II) ions turned out to be more effective against prostate cancer than the ligands themselves [ 6 ]. A novel approach to cancer treatment is targeted therapy, which focuses on inhibiting a specific molecular target.…”

Section: Introductionmentioning

confidence: 99%

Potential Anticancer Agents against Melanoma Cells Based on an As-Synthesized Thiosemicarbazide Derivative

et al. 2022

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In this paper, thiosemicarbazide derivatives were synthesized as potential anticancer agents. X-ray investigations for 1-(2,4-dichlorophenoxy)acetyl-4-(2-fluorophenyl) thiosemicarbazide, 1-(2,4-dichlorophenoxy)acetyl-4-(4-metylothiophenyl)thiosemicarbazide and 1-(2,4-di chlorophenoxy)acetyl-4-(4-iodophenyl)thiosemicarbazide were carried out in order to confirm the synthesis pathways, identify their tautomeric forms, analyze the conformational preferences of molecules, and identify intra- and intermolecular interactions in the crystalline state. TLC and RP-HPLC analyses were used to determine lipophilicity. The lipophilicity analysis revealed that the 4-substituted halogen derivatives of thiosemicarbazides showed greater lipophilicity compared with 2-substituted derivatives. The optimal range of lipophilicity for biologically active compounds logkw is between 4.14 and 4.78. However, as the analysis showed, it is not a decisive parameter. The cytotoxicity of the new compounds was evaluated against both the G-361 and BJ cell lines. Cytotoxicity analyses and cell-cycle and cell apoptosis assays were performed. The MTT test demonstrated that three compounds were cytotoxic to melanoma cells and not toxic to normal fibroblasts in the concentration range used. The cell cycle analysis showed that the compounds had no significant effect on the cell cycle inhibition. An extensive gene expression analysis additionally revealed that all compounds tested downregulated the expression of dihydroorotate dehydrogenase (DHODH). DHODH is a mitochondrial enzyme involved in the de novo synthesis of pyrimidines. Due to the rapid rate of cancer cell proliferation and the increased demand for nucleotide synthesis, it has become a potential therapeutic target.

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Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells

Cited by 30 publications

References 43 publications

Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine

Potential Anticancer Agents against Melanoma Cells Based on an As-Synthesized Thiosemicarbazide Derivative

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