A p r i l 2 2 - 2 3 , 2 0 1 9
A t h e n s , G r e e c e
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Archives of Clinical Microbiology
ISSN: 1989-8436
Virology and Infectious Diseases 2019
EuroSciCon Conference on
Virology and Infectious Diseases
C
hagasdiseaseisasystemicandendemicaneglectedtropicaldisease,
caused by T. cruzi, an obligate intracellular parasite. Nowadays, 8-10
million people in Latin America suffer with this trypanosomiasis and it is
considered a major parasitic disease burden in the American continent.
The treatment is based on two nitroheterocyclic compounds and both
are ineffective against late chronic phase of the disease. Besides, the
toxicity of these compounds is high. Thus, the need for more efficient,
safe, and accessible drugs is urgent. Phospholipids analogues (PAs)
have been shown to be effective against malignant mammalian cells and
some pathogenic protozoa as Leishmania. Here, we analyzed the effects
of new phospholipids analogues on the epimastigotes, trypomastigotes
and intracellular amastigotes of T. cruzi. TC 387, TC388, LDT10 and
LDT137 which were able to inhibit the in vitro growth of epimastigotes
and amastigotes with IC50 in the nanomolar range. Trypomastigote
lysis was also observed. Ultrastructural analysis demonstrated that
these compounds affected the parasite’s membranes. Mitochondrial
and Golgi cisternae swelling and the formation of membrane blebs,
ultimately leading to parasite death, were observed. The Golgi complex
of parasites, but not that of the host cells, was affected suggesting a
specificmechanismof action possibly due to interference in two different
phospholipid biosynthesis pathways used in the distinct cell types. Our
observations show that the trypanocidal activity of the PAs investigated
herein is higher than that of previously reported PAs in the literature. In
conclusion, this work shows that these compounds are potent and fast
acting inhibitors of the growth of the proliferative developmental forms
of T. cruzi (associated with several alterations in the parasite structural
organization) and cause lysis of the highly infective trypomastigote
form. The effects observed support the assertion that interference with
the phospholipids of the membranes is important as a potential route
for the development of new therapeutic agents to treat Chagas disease.
Biography
Emile Barrias is a Researcher in the area of optical
microscopy-Inmetro with emphasis on optical microscopy
of biological material. She holds a Bachelor's degree in
Biological Sciences from the Federal University of Rio de
Janeiro (2006), a Master's degree (2008) and a PhD (2014) in
Biological Sciences (Parasitology and Cell Biology Program)
from theFederalUniversityofRiodeJaneiroatCarlosChagas
Filho Institute of Biophysics. She has experience in the areas
of Celullar Biology, with emphasis on Parasitology, Cell
Biology of parasites, working mainly on the following topics:
Trypanosoma cruzi, T. cruzi interaction-host cell and anti-
parasitic chemotherapy using optical microscopy techniques,
super-resolution (STORM, SIM and GSD), transmission
electron microscopy, scanning electron microscopy (SEM),
multiparametric cell sorting and flow cytometry publishing
15 articles in international journals and three book`s chapters.
She participates in the BIPM (Celullar Analysis Working
Group) research group in cellular quantification pilot studies
involving microscopy techniques.
emilebarrias@gmail.com esbarrias@inmetro.gov.brNew phospholipids analogues as candidates to an anti T. cruzi
chemoterapy: in vitro test and ultra-structural analysis
Emile Barrias
1
, Renato Granato
1
, Luiz Romeiro
2
and Wanderley de Souza
3
1
National Institute of Metrology, Standardization and Industrial Quality (Inmetro), Brazil
2
Brasilia University, Brazil
3
Federal University of Rio de Janeiro, Brazil
Emile Barrias et al., Arch Clin Microbiol 2019, Volume:10
DOI: 10.4172/1989-8436-C1-018