Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole
Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)<sub>2</sub>X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1<i>H</i>-imidazole]; X = NO<sub>3</sub><sup>−</sup> (<b>1</b>),...
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/10/3629 |
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| author | Karolina Stryjska Lidia Radko Lilianna Chęcińska Joachim Kusz Andrzej Posyniak Justyn Ochocki |
| author_facet | Karolina Stryjska Lidia Radko Lilianna Chęcińska Joachim Kusz Andrzej Posyniak Justyn Ochocki |
| author_sort | Karolina Stryjska |
| collection | DOAJ |
| description | Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)<sub>2</sub>X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1<i>H</i>-imidazole]; X = NO<sub>3</sub><sup>−</sup> (<b>1</b>), ClO<sub>4</sub><sup>−</sup> (<b>2</b>)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, <sup>1</sup>H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26–0.47 μM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:42:20Z |
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| spelling | doaj.art-f045b3f4bc4f45f6b3c091a26d910e002023-11-20T01:11:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110362910.3390/ijms21103629Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of MiconazoleKarolina Stryjska0Lidia Radko1Lilianna Chęcińska2Joachim Kusz3Andrzej Posyniak4Justyn Ochocki5Department of Bioinorganic Chemistry, Chair of Medicinal Chemistry, Medical University of Lodz, Muszyńskiego 1, 90-151 Łódź, PolandDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, PolandFaculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Łódź, PolandInstitute of Physics, University of Silesia, 75 Pułku Piechoty 1, 41-500 Chorzów, PolandDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, PolandDepartment of Bioinorganic Chemistry, Chair of Medicinal Chemistry, Medical University of Lodz, Muszyńskiego 1, 90-151 Łódź, PolandTwo novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)<sub>2</sub>X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1<i>H</i>-imidazole]; X = NO<sub>3</sub><sup>−</sup> (<b>1</b>), ClO<sub>4</sub><sup>−</sup> (<b>2</b>)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, <sup>1</sup>H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26–0.47 μM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents.https://www.mdpi.com/1422-0067/21/10/3629silver(I) complexcytotoxicityNMR spectroscopyIR spectroscopyX-ray crystallographyBalb/c 3T3 cell line |
| spellingShingle | Karolina Stryjska Lidia Radko Lilianna Chęcińska Joachim Kusz Andrzej Posyniak Justyn Ochocki Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole International Journal of Molecular Sciences silver(I) complex cytotoxicity NMR spectroscopy IR spectroscopy X-ray crystallography Balb/c 3T3 cell line |
| title | Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole |
| title_full | Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole |
| title_fullStr | Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole |
| title_full_unstemmed | Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole |
| title_short | Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole |
| title_sort | synthesis spectroscopy light stability single crystal analysis and in vitro cytotoxic activity on hepg2 liver cancer of two novel silver i complexes of miconazole |
| topic | silver(I) complex cytotoxicity NMR spectroscopy IR spectroscopy X-ray crystallography Balb/c 3T3 cell line |
| url | https://www.mdpi.com/1422-0067/21/10/3629 |
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