Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes
Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2076-3417/10/14/4846 |
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| author | Přemysl Mladěnka Jana Karlíčková Marcel Hrubša Elma Veljović Samija Muratović Alejandro Carazo Akash Shivling Mali Selma Špirtović-Halilović Luciano Saso Milan Pour Kemal Durić |
| author_facet | Přemysl Mladěnka Jana Karlíčková Marcel Hrubša Elma Veljović Samija Muratović Alejandro Carazo Akash Shivling Mali Selma Špirtović-Halilović Luciano Saso Milan Pour Kemal Durić |
| author_sort | Přemysl Mladěnka |
| collection | DOAJ |
| description | Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity. |
| first_indexed | 2024-03-10T18:29:12Z |
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| id | doaj.art-f793e56e3fbd40ef9aeb2ee8a6b2097e |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T18:29:12Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-f793e56e3fbd40ef9aeb2ee8a6b2097e2023-11-20T06:48:04ZengMDPI AGApplied Sciences2076-34172020-07-011014484610.3390/app10144846Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and ErythrocytesPřemysl Mladěnka0Jana Karlíčková1Marcel Hrubša2Elma Veljović3Samija Muratović4Alejandro Carazo5Akash Shivling Mali6Selma Špirtović-Halilović7Luciano Saso8Milan Pour9Kemal Durić10Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, Albertov 2038/6, 12800 Prague—Nové Město, Czech RepublicDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Organic and Biorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech RepublicDepartment of Pharmacognosy, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and HerzegovinaMetal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.https://www.mdpi.com/2076-3417/10/14/4846transition metalchelationreductionxanthenestructure–activity relationship |
| spellingShingle | Přemysl Mladěnka Jana Karlíčková Marcel Hrubša Elma Veljović Samija Muratović Alejandro Carazo Akash Shivling Mali Selma Špirtović-Halilović Luciano Saso Milan Pour Kemal Durić Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes Applied Sciences transition metal chelation reduction xanthene structure–activity relationship |
| title | Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes |
| title_full | Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes |
| title_fullStr | Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes |
| title_full_unstemmed | Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes |
| title_short | Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes |
| title_sort | interaction of 2 6 7 trihydroxy xanthene 3 ones with iron and copper and biological effect of the most active derivative on breast cancer cells and erythrocytes |
| topic | transition metal chelation reduction xanthene structure–activity relationship |
| url | https://www.mdpi.com/2076-3417/10/14/4846 |
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