In vitro effects of benzimidazole/thioether-copper complexes with antitumor activity on human erythrocytes
| Autor: | Edelmiro Santiago-Osorio, Mario Suwalsky, Itzen Aguiñiga, Brenda N. Sánchez-Eguía, María José Gallardo, Ana Rocío Rivera-Martínez, Ivan Castillo, Nathan Dukes |
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| Rok vydání: | 2018 |
| Předmět: |
Steric effects
Erythrocytes Stereochemistry Antineoplastic Agents Sulfides 010402 general chemistry 01 natural sciences Biochemistry Inorganic Chemistry Cell membrane Inhibitory Concentration 50 chemistry.chemical_compound X-Ray Diffraction Thioether Coordination Complexes Cell Line Tumor medicine Humans Moiety Cell Proliferation Molecular Structure 010405 organic chemistry Chemistry Bilayer 0104 chemical sciences Crystallography medicine.anatomical_structure Membrane Lipophilicity Microscopy Electron Scanning Benzimidazoles Amine gas treating Copper |
| Zdroj: | Journal of Inorganic Biochemistry. 178:87-93 |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2017.10.009 |
| Popis: | Two cytotoxic copper(II) complexes with N-H and N-methylated benzimidazole-derived ligands (Cu-L1 and Cu-L1Me; L1=bis(2-methylbenzimidazolyl)(2-methylthioethyl)amine, L1Me=bis(1-methyl-2-methylbenzimidazolyl)(2-methylthioethyl)amine) were synthesized and exposed to human erythrocytes and molecular models of its membrane. The latter were bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), classes of lipids present in the external and internal moieties of the human red cell membrane, respectively. Scanning electron microscopy (SEM) of erythrocytes incubated with solutions of both Cu(II) complexes showed that they induced morphological changes to the normal cells to echinocytes, and hemolysis at higher concentrations. Real-time observation of the dose-dependent effects of the complexes on live erythrocytes by defocusing microscopy (DM) confirmed SEM results. The formation of echinocytes implied that complex molecules inserted into the outer moiety of the red cell membrane. X-ray diffraction studies on DMPC and DMPE showed that none of these complexes interacted with DMPE and only Cu-L1 interacted with DMPC. This difference was explained by the fact that Cu-L1Me complex is more voluminous than Cu-L1 because it has two additional methyl groups; on the other hand, DMPC molecule has three methyl groups in its bulky terminal amino end. Thus, by steric hindrance Cu-L1Me molecules cannot intercalate into DMPC bilayer, which besides is present in the gel phase. These results, together with the increased antiproliferative capacity of the N-methylated complex Cu-L1Me over that of Cu-L1 are rationalized mainly based on its higher lipophilicity. |
| Databáze: | OpenAIRE |
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