In vivo studies of the effectiveness of novel N-halomethylated and non-halomethylated quaternary ammonium salts in the topical treatment of cutaneous leishmaniasis.

Abstract

The physicochemical properties of four N-halomethylated and one non-halomethylated ammonium salts, with proven in vitro antileishmanial activity, were determined according to pharmaceutical standard procedures. The effectiveness and toxicity of these compounds were assessed in hamsters infected with Leishmania (Viannia) braziliensis and compared to that showed by meglumine antimoniate. Animals were followed during 90days after the completion of treatment. Therapeutic response was determined according to the reduction of size of skin lesions. Toxicity was determined by the effect of compounds on body weight changes and serum levels of renal and hepatic metabolites. The effectiveness of compound 4 was similar to that showed by intralesional administration of meglumine antimoniate and better than that of the other ammonium salts. Levels of creatinine, alanine amino transferase, and blood urea nitrogen in serum were not significantly different between treatment groups, including healthy or untreated hamsters. Results imply that compound 4 has potential as a pharmaceutical active ingredient in the development of new and better formulations for the treatment of cutaneous leishmaniasis.