The benzodiazepine class of compounds as a potential for the treatment of cutaneous leishmaniasis

Abstract

Cutaneous leishmaniasis is endemic in over 70 countries in the tropics and neotropics. Several Leishmania species are the causative agent of this form of the disease and are transmitted to humans and animals by a bite of a phlebotomies sandfly. Antileishmanial drugs including antimonials, Amphotericin B, pentamidine, paromomycin, allupurinol and miltefosine have been the treatment of choice over recent years. However, toxicity, difficulty of administration and emergence of resistance have limited the number of chemotherapeutic options available hence underlying the urgency for the identification of new classes of compounds with antileishmanial activity. The benzodiazepine class of compounds whose core structure entails the fusion of a benzene and diazepine ring have been used over the past 50 years as psychoactive drugs in the treatment of anxiety, insomnia and as an anticonvulsants. The aim of this study was to explore the antileishmanial effects of this class of compounds on stationary phase promastigotes of old and new world Leishmania species (L. aethiopica, L. major, L. tropica and L. mexicana) using the 3-(4,5-dimethylthiazol+2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay for assessing parasite viability. An array of compounds with modifications brought about at the benzene and diazepine structures were tested over a range of concentrations over a 24-hour period for all species mentioned above. The three most active compounds (RRP223, RRP262 and RRP 199) displayed a different range of activity with inhibition of parasite growth at micromolar range in all 4 species. These findings implicate selective activity and demonstrate Leishmanicidal potential in the benzodiazepine class of compounds