Thiourea Modified Doxorubicin: A Perspective pH-Sensitive Prodrug
| Autor: | Pavel A. Ignatov, Pavel A. Panchenko, Svetlana V Lavrushkina, Igor I. Kireev, Vladislav M Malinnikov, Elena K. Beloglazkina, Irina V. Grishina, Sergey S Kovalev, Nikolay V. Zyk, Olga O. Krasnovskaya, Dmitry A. Skvortsov, Vasily M. Gerasimov, Marina A. Zakharko, Olga A. Fedorova, Alexander G. Majouga, Natalia S Dashkova, Gediminas Jonusauskas |
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| Přispěvatelé: | Laboratoire de Biologie cellulaire et Microscopie Electronique, Université Francois Rabelais [Tours], Department of Chemistry, Lomonosov Moscow State University (MSU), Laboratoire Ondes et Matière d'Aquitaine (LOMA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Département Décision en Entreprise : Modélisation, Optimisation (DEMO-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Henri Fayol |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Biomedical Engineering Pharmaceutical Science Bioengineering 02 engineering and technology Naphthalenes 01 natural sciences chemistry.chemical_compound Cell Line Tumor Fluorescence Resonance Energy Transfer medicine Humans Cytotoxic T cell Prodrugs Doxorubicin Cytotoxicity IC50 Pharmacology [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics] Antibiotics Antineoplastic 010405 organic chemistry Chemistry Organic Chemistry Thiourea Prostatic Neoplasms Biological activity Hydrogen-Ion Concentration Prodrug 021001 nanoscience & nanotechnology Combinatorial chemistry 0104 chemical sciences 3. Good health Cancer cell Fluorescein [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph] 0210 nano-technology Biotechnology medicine.drug |
| Zdroj: | Bioconjugate Chemistry Bioconjugate Chemistry, American Chemical Society, 2019, 30 (3), pp.741-750. ⟨10.1021/acs.bioconjchem.8b00885⟩ |
| ISSN: | 1043-1802 1520-4812 |
| DOI: | 10.1021/acs.bioconjchem.8b00885⟩ |
| Popis: | International audience; A novel approach to the synthesis of pH-sensitive prodrugs has been proposed: thiourea drug modification. Resulting prodrugs can release the cytotoxic agent and the biologically active 2-thiohydantoin in the acidic environment of tumor cells. The concept of acid-catalyzed cyclization of thioureas to 2-thiohydantoins has been proven using a FRET model. Dual prodrugs of model azidothymidine, cytotoxic doxorubicin, and 2-thiohydantoin albutoin were obtained, which release the corresponding drugs in the acidic environment. The resulting doxorubicin prodrug was tested on prostate cancer cells and showed that the thiourea-modified prodrug is less cytotoxic (average IC50 ranging from 0.5584 to 0.9885 μM) than doxorubicin (IC50 ranging from 0.01258 to 0.02559 μM) in neutral pH 7.6 and has similar toxicity (average IC50 ranging from 0.4970 to 0.7994 μM) to doxorubicin (IC50 ranging from 0.2303 to 0.8110 μM) under mildly acidic conditions of cancer cells. Cellular and nuclear accumulation in PC3 tumor cells of Dox prodrug is much higher than accumulation of free doxorubicin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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