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
Source abstract
Abstract
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.
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Research context
OpenAlex topics: Trace Elements in Health · Hemoglobinopathies and Related Disorders · Drug Transport and Resistance Mechanisms
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech Republic
Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech Republic
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina
Department of Physiology, Faculty of Science, Charles University, Albertov 2038/6, 12800 Prague—Nové Město, Czech Republic
Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Department of Organic and Biorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Ak. Heyrovského 1203, 50005 Hradec Králové, Czech Republic
Department of Pharmacognosy, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina
Funding
EFSA-CDN
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