Activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis

Abstract

The currently used treatments for leishmaniasis, a neglected parasitic disease, are associated with several side effects, high cost and resistance of the Leishmania parasites. Here we evaluated in vitro and in vivo the antileishmanial activity of five antimalarial drugs against Leishmania amazonensis. Mefloquine was effective against promastigotes in axenic cultures and showed an IC 50 (concentration giving half-maximal inhibition) value of 8.4±0.7 mM. In addition, mefloquine, chloroquine and hydroxychloroquine were active against intracellular amastigotes in macrophageinfected cultures, presenting IC 50 values of 1.56±0.19 mM, 0.78±0.08 mM and 0.67±0.12 mM, respectively. The ultrastructural analysis of chloroquine-or mefloquine-treated amastigotes showed an accumulation of multivesicular bodies in the cytoplasm of the parasite, suggesting endocytic pathway impairment, in addition to the formation of myelin-like figures and enlargement of the Golgi cisternae. CBA mice were infected with L. amazonensis in the ear dermis, and treated by oral and/or topical routes with chloroquine and mefloquine. Treatment of L. amazonensisinfected mice with chloroquine by the oral route reduced lesion size, which was associated with a decrease in the number of parasites in the ear, as well as the parasite burden in the draining lymph nodes. In contrast, mefloquine administration by both routes decreased the lesion size in infected mice without causing a reduction in parasite burden. Our results revealed a promising antileishmanial effect of chloroquine and suggest its use in cutaneous leishmaniasis treatment.

Efficacy of Paromomycin-Chloroquine Combination Therapy in Experimental Cutaneous Leishmaniasis

“…Furthermore, antileishmanial activity of CQ in the L. amazonensis CBA mouse ear model has been reported, although this was observed after higher-dose oral treatment (50 mg/kg) over longer periods (5 weeks) (27). …”

Antiparasitic activities of novel ruthenium/lapachol complexes

“…For comparison, the metal-free lapachol was included in the pharmacological evaluation. Firstly, compounds were evaluated on their ability to inhibit the L. amazonensis promastigote proliferation, as well as against intracellular amastigotes, according to standard methodology [33]. Secondly, the antimalarial activity of the complexes was determined against the erythrocytic stage of W2 strain P. falciparum.…”

The efficacy of 2-nitrovinylfuran derivatives againstLeishmania in vitro and in vivo

“…This effect could also be visualised as the loss of parasite motility after 2-3 h of exposure. IC 50 values estimated for the 2-nitrovinylfurans were comparable to those of standard antileishmanial drugs as well as of active investigational compounds in the promastigote screening system (Vermeersch et al 2009, Hazra et al 2012 , Rocha et al 2013 ).…”