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Ferrocene-embedded flavonoids targeting the Achilles heel of multidrug-resistant cancer cells through collateral sensitivity
- Source :
- European journal of medicinal chemistry. 130
- Publication Year :
- 2016
-
Abstract
- With the aim to develop anticancer agents acting selectively against resistant tumor cells, we investigated ferrocene embedded into chalcone, aurone and flavone skeletons. These compounds were conceived and then investigated based on the concept of collateral sensitivity, where the target is the Achilles Heel of cancer cells overexpressing the multidrug ABC transporter MRP1. The 14 synthesized compounds were evaluated for their ability to induce efflux of glutathione (GSH) from tumor cells overexpressing MRP1. When tested at 5 and 20 μM, at least one compound from each series was found to be a highly inducer of GSH efflux. The different compounds inducing a high efflux of GSH were evaluated on both sensitive and resistant cell lines, and two of them, belonging to the flavones class were found to be more cytotoxic on resistant cancer cells, with the best selectivity ratio >9.1. Our results bring chemical and biological bases for further optimization.
- Subjects :
- 0301 basic medicine
Chalcone
Metallocenes
Antineoplastic Agents
Flavones
Sensitivity and Specificity
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
Aurone
Cytotoxic T cell
Humans
Ferrous Compounds
Pharmacology
chemistry.chemical_classification
Flavonoids
Cytotoxins
Organic Chemistry
General Medicine
Glutathione
Drug Resistance, Multiple
030104 developmental biology
Biochemistry
chemistry
Cell culture
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Efflux
Multidrug Resistance-Associated Proteins
Subjects
Details
- ISSN :
- 17683254
- Volume :
- 130
- Database :
- OpenAIRE
- Journal :
- European journal of medicinal chemistry
- Accession number :
- edsair.doi.dedup.....e93e359fed57b885bca739aabd5f7552