The alkylaminoalkanethiosulfuric acids exhibit in‐vitro in‐vitro antileishmanial activity against Leishmania (Viannia) braziliensis Leishmania (Viannia) braziliensis : a new perspective for use of these schistosomicidal agents

摘要

Abstract The alkylaminoalkanethiosulfuric acids (AAATs) are amphipathic compounds effective against experimental schistosomiasis, of low toxicity, elevated bioavailability after a single oral dose and prompt tissue absorption. Objectives To explore the in‐vitro antileishmanial potential of AAATs using five compounds of this series against Leishmania ( Viannia ) braziliensis . Methods Their effects on promastigotes and axenic amastigotes, and cytotoxicity to macrophages were tested by the MTT method, and on Leishmania ‐infected macrophages by Giemsa stain. Effects on the mitochondrial membrane potential of promastigotes and axenic amastigotes and DNA of intracellular amastigotes were tested using JC‐1 and TUNEL assays, respectively. Key findings The 2‐(isopropylamino)‐1‐octanethiosulfuric acid (I) and 2‐( sec ‐butylamino)‐1‐octanethiosulfuric acid (II) exhibit activity against both promastigotes and intracellular amastigotes (IC 50 25‐35?μm), being more toxic to intracellular parasites than to the host cell. Compound I induced a loss of viability of axenic amastigotes, significantly reduced (30%) the mitochondrial membrane potential of both promastigotes and axenic amastigotes and promoted selective DNA fragmentation of the nucleus and kinetoplast of intracellular amastigotes. Conclusions In this previously unpublished study of trypanosomatids, it is shown that AAATs could also exhibit selective antileishmanial activity, a new possibility to be investigated in oral treatment of leishmaniasis.