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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 21; p. 5075
• Main Authors: Feng, Liwen, Pomel, Sébastien, Latre de Late, Perle, Taravaud, Alexandre, Loiseau, Philippe M, Maes, Louis, Cho-Ngwa, Fidelis, Bulman, Christina A, Fischer, Chelsea, Sakanari, Judy A, Ziniel, Peter D, Williams, David L, Davioud-Charvet, Elisabeth
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2020; MDPI
• Subjects: Amastigotes; Animals; Anthelmintics - chemistry; Anthelmintics - pharmacology; anti-amoeba; anti-helminth; anti-leishmanial; anti-trypanosomal; anticancer; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antiparasitic; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Auranofin - chemistry; Auranofin - pharmacology; Bacterial infections; Bioavailability; Brain tumors; Breast; Cattle; Cell Line, Tumor; Chemical Sciences; Coordination chemistry; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Drug Evaluation; Drug resistance; Enzymes; Gold; Gold - chemistry; Gold - pharmacology; Helminthiasis - drug therapy; Helminthiasis - metabolism; Helminthiasis - pathology; Humans; Infections; Life Sciences; Ligands; Medication; Metabolism; Molecular weight; Nematodes; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Oral administration; Organic chemistry; Parasites; Parasitic diseases; Pharmaceutical sciences; Proteins; Protozoa; Protozoan Infections - drug therapy; Protozoan Infections - metabolism; Protozoan Infections - pathology; Public health; Reductases; Selenium; Thioredoxin; Tropical diseases; Worms; anti-leishmanial; auranofin; gold(I) complex; thioredoxin; glutathione; antiparasitic; anti-amoeba; anti-helminth; anti-trypanosomal; anticancer; redox equilibrium
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25215075

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-β-d-glucopyranose 2,3,4,6-tetraacetato- -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-protozoans, trematodes, and nematodes-was undertaken to determine the in vitro killing activity of GoPI-sugar compared to auranofin. GoPI-sugar was found to efficiently kill intramacrophagic amastigotes and adult filarial and trematode worms.