Elucidating the possible mechanism of action of some pathogen box compounds against Leishmania donovani
Date
2020-04-10
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS NEGLECTED TROPICAL DISEASES
Abstract
Leishmaniasis is one of the Neglected Tropical Diseases (NTDs) which is closely associated
with poverty and has gained much relevance recently due to its opportunistic coinfection
with HIV. It is a protozoan zoonotic disease transmitted by a dipteran Phlebotomus, Lutzomyia/
Sergentomyia sandfly; during blood meals on its vertebrate intermediate hosts. It is a
four-faceted disease with its visceral form being more deadly if left untreated. It is endemic
across the tropics and sub-tropical regions of the world. It can be considered the third most
important NTD after malaria and lymphatic filariasis. Currently, there are numerous drawbacks
on the fight against leishmaniasis which includes: non-availability of vaccines, limited
availability of drugs, high cost of mainstay drugs and parasite resistance to current treatments.
In this study, we screened the antileishmanial activity, selectivity, morphological
alterations, cell cycle progression and apoptotic potentials of six Pathogen box compounds
from Medicine for Malaria Venture (MMV) against Leishmania donovani promastigotes and
amastigotes. From this study, five of the compounds showed great promise as lead chemotherapeutics
based on their high selectivity against the Leishmania donovani parasite when
tested against the murine mammalian macrophage RAW 264.7 cell line (with a therapeutic
index ranging between 19–914 (promastigotes) and 1–453 (amastigotes)). The cell cycle
progression showed growth arrest at the G0-G1 phase of mitotic division, with an indication
of apoptosis induced by two (2) of the pathogen box compounds tested. Our findings present
useful information on the therapeutic potential of these compounds in leishmaniasis. We
recommend further in vivo studies on these compounds to substantiate observations made
in the in vitro study.
Description
Research Article
Keywords
leishmaniasis, Neglected Tropical Diseases (NTDs), sub-tropical regions, Medicine for Malaria Venture (MMV)
Citation
Amlabu WE, Antwi CA, Awandare G, Gwira TM (2020) Elucidating the possible mechanism of action of some pathogen box compounds against Leishmania donovani. PLoS Negl Trop Dis 14(4): e0008188. https://doi. org/10.1371/journal.pntd.0008188