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
Liwen Feng,
Sébastien Pomel,
Perle Latre de Late,
Alexandre Taravaud,
Philippe M. Loiseau,
Louis Maes,
Fidelis Cho-Ngwa,
Christina A. Bulman,
Chelsea Fischer,
Judy A. Sakanari,
Peter D. Ziniel,
David L. Williams,
Elisabeth Davioud-Charvet
Affiliations
Liwen Feng
UMR 7042 CNRS-Université de Strasbourg-Université Haute-Alsace, Laboratoire d’Innovation Moléculaire et Applications (LIMA), Bioorganic and Medicinal Chemistry Team, European School of Chemistry, Polymers and Materials (ECPM), 25, rue Becquerel, F-67087 Strasbourg, France
Sébastien Pomel
BioCIS, Faculty of Pharmacy, Université Paris-Saclay, CNRS, 92290 Châtenay-Malabry, France
Perle Latre de Late
INSERM U1016, CNRS UMR 8104, Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Cochin Institute, Faculté de Medecine, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France
Alexandre Taravaud
BioCIS, Faculty of Pharmacy, Université Paris-Saclay, CNRS, 92290 Châtenay-Malabry, France
Philippe M. Loiseau
BioCIS, Faculty of Pharmacy, Université Paris-Saclay, CNRS, 92290 Châtenay-Malabry, France
Louis Maes
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
Fidelis Cho-Ngwa
Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon
Christina A. Bulman
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA
Chelsea Fischer
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA
Judy A. Sakanari
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA
Peter D. Ziniel
Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA
David L. Williams
Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA
Elisabeth Davioud-Charvet
UMR 7042 CNRS-Université de Strasbourg-Université Haute-Alsace, Laboratoire d’Innovation Moléculaire et Applications (LIMA), Bioorganic and Medicinal Chemistry Team, European School of Chemistry, Polymers and Materials (ECPM), 25, rue Becquerel, F-67087 Strasbourg, France
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-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—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 Leishmania donovani amastigotes and adult filarial and trematode worms.
