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

• Published in: Journal of pharmacy and pharmacology Vol. 71; no. 12; p. 1784
• Main Authors: Porcino, Gabriane Nascimento, Antinarelli, Luciana Maria Ribeiro, Maia, Ana Carolina Ribeiro Gomes, Faria-Pinto, Priscila, Taunay-Rodrigues, Alessandro, Zech Coelho, Paulo Marcos, Nelson, David Lee, Penido, Marcus Luiz Oliveira, Coimbra, Elaine Soares, Vasconcelos, Eveline Gomes
• Format: Journal Article
• Language: English
• Published: England 01.12.2019
• Subjects: Administration, Oral; Animals; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Inhibitory Concentration 50; Leishmania braziliensis - drug effects; Leishmania braziliensis - isolation & purification; Leishmaniasis - drug therapy; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Inbred BALB C; Structure-Activity Relationship; Sulfuric Acids - administration & dosage; Sulfuric Acids - chemistry; Sulfuric Acids - pharmacology; alkylaminoalkanethiosulfuric acids; trypanosomatids; antileishmanial; leishmaniasis
• ISSN: 2042-7158
• DOI: 10.1111/jphp.13163

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. To explore the in-vitro antileishmanial potential of AAATs using five compounds of this series against Leishmania (Viannia) braziliensis. 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. The 2-(isopropylamino)-1-octanethiosulfuric acid (I) and 2-(sec-butylamino)-1-octanethiosulfuric acid (II) exhibit activity against both promastigotes and intracellular amastigotes (IC 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. 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.