Biological Activity and Structure–Activity Relationship of Functionalized Thiols Against <i>Leishmania major</i>, the Agent of Human Cutaneous Leishmaniasis

Abstract

Leishmania is a protozoan parasite causing a spectrum of pathologies in humans grouped under the name leishmaniasis. Clinical outcomes range from the self-healing cutaneous form to the visceral one that is fatal in the absence of treatment. The leishmaniases are endemic in 98 countries in the tropics, subtropics, and Southern Europe, where 3 million new cases and more than 50,000 deaths are recorded yearly. Control of this disease is challenging as there is no approved vaccine coupled with toxic chemotherapeutics and the development of parasite resistance to some available drugs. It is, therefore, evident that the identification of new control methods, including new therapeutics, should be strongly encouraged. In the present study, thiol organic compounds were synthesized and tested for their activity against Leishmania major, the causative agent of human cutaneous leishmaniasis. Of the 21 compounds tested, 13 were active against L. major promastigotes in vitro at 100 μg/mL. Selected compounds tested in a dose-response assay showed activity at concentration as low as 25 μg/mL, a level of activity similar to that of Amphotericin B, a drug of choice for the treatment of human leishmaniasis. Structure–activity analysis shows that the addition of certain substituents, such as a methoxy group, to a compound that is biologically active renders it inactive. Together, our data demonstrate that functionalized thiols have an in vivo anti-Leishmania activity that is directly linked to their chemical structure.

Keywords

• leishmaniasis
• <i>Leishmania major</i>
• functionalized thiols
• antileishmanial activity