Susceptibility of Leishmania (Leishmania) amazonensis to
antimalarials: An alternative for the in vivo study of drug repositioning
Leishmania (L.) amazonensis, antimalarial, leishmanicidal, drug
combination.
Leishmaniasis are endemic parasitic diseases that concern Brazilian public health. The
state of Rondônia is an area of transmission of the disease with an average incidence
of 975 cases between the years 2016 and 2020. for the urgency of new therapeutic
drugs. The repositioning of drugs with confirmed action against other protozoa can
accelerate the discovery of therapeutic alternatives for leishmaniasis, and expand the
market for the product whose toxicological description has already been forwarded to
the drug regulatory authorities. Recent in vitro tests of anti-promastigotes and anti-
amastigote of Leishmania, carried out by our group of researchers, demonstrated the
leishmanicidal action of some antimalarials, resulting in the design of this study. The
objective of this study is to evaluate the in vivo susceptibility profile of Leishmania
(Leishmania) amazonensis to antimalarials alone or in combination with reference
drugs for leishmaniasis recommended in Brazil. With the infection of Balb/c mice with
the parasite, it was possible to verify the parasitic load of the lesion on the paws,
obtaining the effective dose for killing 50% of the parasite (DE50) of amphotericin B
(0.63 mg/Kg), artesunate (3.13 mg/Kg) and chloroquine (27.29 mg/Kg). With these
data, it was possible to perform a combination of antimalarials with amphotericin B,
and they obtained opposite results, while in the combination with artesunate there was
an increase in parasitemia, the combination with chloroquine occurred a decrease, the
latter despite not having a total cure was statistically equal to the naive group. In this
study, the dosage of cytokines and biochemical metabolites in serum will be quantified
using commercial kits. The perspectives of this study are to expand the alternatives of
chemotherapy formulations and predict the rational use of drugs, aiming to avoid the
existing limitations.