Future prospects in the treatment of parasitic diseases: 2-amino-1,3,4-thiadiazoles in leishmaniasis

Abstract

Neglected tropical diseases affect the lives of a billion people worldwide. Among them, the parasitic infections caused by protozoan parasites of the Trypanosomatidae family have a huge impact on human health. Leishmaniasis, caused by Leishmania spp., is an endemic parasitic disease in over 88 countries and is closely associated with poverty. Although significant advances have been made in the treatment of leishmaniasis over the last decade, currently available chemotherapy is far from satisfactory. The lack of an approved vaccine, effective medication and significant drug resistance worldwide had led to considerable interest in discovering new, inexpensive, efficient and safe antileishmanial agents. 1,3,4-Thiadiazole rings are found in biologically active natural products and medicinally important synthetic compounds. The thiadiazole ring exhibits several specific properties: it is a bioisostere of pyrimidine or benzene rings with prevalence in biologically active compounds; the sulfur atom increases lipophilicity and combined with the mesoionic character of thiadiazoles imparts good oral absorption and good cell permeability, resulting in good bioavailability. This review presents synthetic 2-amino-1,3,4-thiadiazole derivatives with antileishmanial activity. Many reported derivatives can be considered as lead compounds for the synthesis of future agents as an alternative to the treatment of leishmaniasis.