Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation

Paola Baiocco; Andrea Ilari; Pierpaolo Ceci; Stefania Orsini; Marina Gramiccia; Trentina Di Muccio; Gianni Colotti

doi:10.1021/ml1002629

Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation

ACS Med Chem Lett. 2010 Dec 29;2(3):230-3. doi: 10.1021/ml1002629. eCollection 2011 Mar 10.

Authors

Paola Baiocco¹, Andrea Ilari¹, Pierpaolo Ceci¹, Stefania Orsini², Marina Gramiccia², Trentina Di Muccio², Gianni Colotti¹

Affiliations

¹ Institute of Molecular Biology and Pathology CNR, and Department of Biochemical Sciences, Sapienza University of Roma , P.le A. Moro 5, 00185 Rome, Italy.
² Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità , Viale Regina Elena 299, 00161 Rome, Italy.

Abstract

In Leishmania the glutathione/glutathione reductase eukaryotic redox sys-tem is replaced by the unique trypanothione/trypanothione reductase (TR) system. In vitro, silver is a more effective TR inhibitor than antimony, the first line drug against leishmaniasis in most endemic countries, and its mechanism of inhibition is similar to that of Sb(III). In particular, silver binds with high affinity to the catalytic triad Cys52, Cys57, and His461', thereby inhibiting TR. Here, Ag(0) activity was tested on the promastigote and amastigote stages of Leishmania infantum using a drug-delivery system consisting in Ag(0) nanoparticles encapsulated by ferritin molecules (PfFt-AgNPs). These were able to induce an antiproliferative effect on the parasites at metal concentrations lower than those used with antimony.

Keywords: Leishmania; Trypanothione reductase; drug delivery; nanoparticles; silver.