title: Biochemical effects of riluzole on Leishmania parasites.
abstract: We have previously shown that riluzole (6-(trifluoromethoxy)benzothiazol-2-amine), an agent used to treat CNS disorders, possesses inhibitory activity against pteridine reductase (PTR1) in pathogenic protists at low micromolar concentrations. Therefore, the potential use of this drug in anti-parasitic chemotherapy deserves evaluation. In this study, we report the effect of this compound on cell cultures of Leishmania mexicana and L. major. The anti-parasitic activity of riluzole was confirmed, with the largest effect observed when the drug was administered to cells during their exponential growth phase. Moreover, a remarkable decrease in PTR1 activity was observed in the lysates of cells pretreated with the compound, which is due to impairment of the enzyme's preferential reaction with biopterin as a cofactor. In addition, the treatment increased the parasites' susceptibility to oxidative stress, affecting the ability of Leishmania to survive under severe oxidative conditions. These results suggest that the inhibitory effect of riluzole on PTR1 is not the only mechanism through which it induces the death of Leishmania parasites.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. davide.guerrieri@nih.gov
authors.forename: Davide
authors.initials: D
authors.lastname: Guerrieri
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.forename: M Paola
authors.initials: MP
authors.lastname: Costi
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Michels
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018320:Leishmania major / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D007894:Leishmania mexicana / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011739:Pyrimethamine / Q000494:pharmacology; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019782:Riluzole; D010088:Oxidoreductases; C085592:pteridine reductase; D011739:Pyrimethamine