Abstract
In the midst of numerous setbacks that beclouds the fight against leishmaniasis; a neglected tropical disease, the search for new chemotherapeutics against this disease is of utmost importance. Leishmaniasis is a disease closely associated with poverty and endemic in Africa, Asia, southern Europe and the Americas. It is caused by parasites of the genus Leishmania and transmitted by a sandfly vector. In this study, we evaluated the antileishmanial potency of eighteen pathogen box compounds and elucidated their biosafety and possible mechanisms of action against Leishmania donovani promastigotes and amastigotes in vitro. IC50s range of 0.12±0.15 to >6.25 μg/ml and 0.13±0.004 to >6.25μg/ml were observed for the promastigotes and amastigotes, respectively. We demonstrated the ability of some of the compounds to cause cytocidal effect on the parasites, induce increased production of reactive oxygen species (ROS), disrupt the normal parasite morphology and cause the accumulation of parasites at the DNA synthesis phase of the cell cycle. We recommend a further in vivo study on these compounds to validate the findings.
Highlights
Leishmania sp. were independently described by William Leishman and Charles Donovan in 1903 and the genus proposed by James Wright in 1903 [1, 2]
We report the bioactive potencies of some selected pathogen box compounds showing growth inhibition and eventual cell death against Leishmania donovani parasites
These parasites were treated with eighteen selected Medicine for Malaria Venture (MMV) compounds and growth inhibitory concentrations (IC50s) ranging from 0.12 –>6.25 μg/ml were recorded against the promastigotes and 0.13- >6.25 μg/ml against the amastigotes stages of the parasite
Summary
Leishmania sp. were independently described by William Leishman and Charles Donovan in 1903 and the genus proposed by James Wright in 1903 [1, 2]. Were independently described by William Leishman and Charles Donovan in 1903 and the genus proposed by James Wright in 1903 [1, 2]. They belong to the Class: Kinetoplastida and Family: Trypanosomatidae. These parasites have a dimorphic life cycle with the organism shuttling between a flagellated free-living promastigote in the gut of the sand fly vector and an intracellular amastigote in the mammalian host [3, 4].
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