Repurposing Auranofin and Evaluation of a New Gold(I) Compound for the Search of Treatment of Human and Cattle Parasitic Diseases: From Protozoa to Helminth Infections
| Autor: | David L. Williams, Peter Ziniel, Christina A. Bulman, Alexandre Taravaud, Fidelis Cho-Ngwa, Liwen Feng, Chelsea Fischer, Sébastien Pomel, Perle Latré de Laté, Philippe M. Loiseau, Louis Maes, Judy A. Sakanari, Elisabeth Davioud-Charvet |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Laboratoire d'innovation moléculaire et applications (LIMA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
anti-trypanosomal
Thioredoxin reductase Helminthiasis Pharmaceutical Science Analytical Chemistry gold(I) complex Coordination Complexes Neoplasms Drug Discovery glutathione ComputingMilieux_MISCELLANEOUS anti-amoeba Anthelmintics 0303 health sciences biology [CHIM.ORGA]Chemical Sciences/Organic chemistry Pharmacology. Therapy auranofin anti-leishmanial 3. Good health Chemistry Chemistry (miscellaneous) anti-helminth Human parasite Molecular Medicine Thioredoxin medicine.drug Auranofin antiparasitic Antiparasitic medicine.drug_class Antiprotozoal Agents Leishmania donovani Antineoplastic Agents anticancer Article Microbiology lcsh:QD241-441 03 medical and health sciences [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication lcsh:Organic chemistry Cell Line Tumor redox equilibrium medicine Animals Humans [CHIM.COOR]Chemical Sciences/Coordination chemistry Physical and Theoretical Chemistry Amastigote Biology 030304 developmental biology Protozoan Infections 030306 microbiology Organic Chemistry thioredoxin biology.organism_classification Drug Evaluation Protozoa Cattle Gold |
| Zdroj: | Molecules, Vol 25, Iss 5075, p 5075 (2020) Molecules Molecules, MDPI, 2020, 25 (21), pp.5075. ⟨10.3390/molecules25215075⟩ Molecules: a journal of synthetic chemistry and natural product chemistry Volume 25 Issue 21 |
| ISSN: | 1420-3049 |
| Popis: | Neglected parasitic diseases remain a major public health issue worldwide, especially in tropical and subtropical areas. Human parasite diversity is very large, ranging from protozoa to worms. In most cases, more effective and new drugs are urgently needed. Previous studies indicated that the gold(I) drug auranofin (Ridaura® ) is effective against several parasites. Among new gold(I) complexes, the phosphole-containing gold(I) complex {1-phenyl-2,5-di(2-pyridyl)phosphole}AuCl (abbreviated as GoPI) is an irreversible inhibitor of both purified human glutathione and thioredoxin reductases. GoPI-sugar is a novel 1-thio-&beta d-glucopyranose 2,3,4,6-tetraacetato-S-derivative that is a chimera of the structures of GoPI and auranofin, designed to improve stability and bioavailability of GoPI. These metal-ligand complexes are of particular interest because of their combined abilities to irreversibly target the essential dithiol/selenol catalytic pair of selenium-dependent thioredoxin reductase activity, and to kill cells from breast and brain tumors. In this work, screening of various parasites&mdash protozoans, trematodes, and nematodes&mdash was undertaken to determine the in vitro killing activity of GoPI-sugar compared to auranofin. GoPI-sugar was found to efficiently kill intramacrophagic Leishmania donovani amastigotes and adult filarial and trematode worms. |
| Databáze: | OpenAIRE |
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