Journal
ACTA TROPICA
Volume 183, Issue -, Pages 36-42Publisher
ELSEVIER
DOI: 10.1016/j.actatropica.2018.03.023
Keywords
Leishmania; 4-Aryloxy-7-chloroquinoline derivatives; Miltefosine; Amphotericin B; Drug combinations; Mitochondrial membrane potential; Synergistic effect
Categories
Funding
- Consejo de Desarrollo Cientifico y Humanistic from the Universidad Central de Venezuela (C.D.C.H.- U.C.V) [PG-03-8289-2011/1, PG 03-8728-2013/2]
- Consejo Nacional de Investigaciones Cientificas y Tecnologicas (FONACIT), Venezuela [2017000274]
Ask authors/readers for more resources
The present study evaluates in vitro the effect of two synthetic compounds of the 7-chloro-4-aryloxyquinoline series, QI (C17H12ClNO3) and QII (C18H15ClN4O2S), on Leishmania donovani parasites. The results obtained demonstrate that these compounds are able to inhibit the proliferation of L. donovani promastigotes in a dose-dependent way (QI IC50 = 13.03 +/- 3.4 and QII IC50 = 7.90 +/- 0.6 mu M). Likewise, these compounds significantly reduced the percentage of macrophage infection by amastigotesand the number of amastigotes within macrophage phagolysosomes, the clinical relevant phase of these parasites. Compound QI showed an IC50 value of 0.66 +/- 0.2 mu M, while for derivative QII, the corresponding IC50 was 1.02 +/- 0.17 mu M. Interestingly, the amastigotes were more susceptible to the drug treatment when compared to promastigotes. Furthermore, no cytotoxic effect of these compounds was observed on the macrophage cell line at the concentrations tested. The combination of these compounds with miltefosine and amphotericin B on both parasite morphotypes was evaluated. The isobolograms showed a synergistic effect for both combinations; with a Fractional Inhibitory Concentration (FIC) Index lower than 1 for promastigotes and less than 0.3 for intracellular amastigotes. The effect of QI and QII on mitochondrial membrane potential was also studied. The combination of quinolone derivatives compounds with miltefosine and amphotericin B showed 5-8-fold stronger depolarization of membrane mitochondrial potential when compared to drugs alone. The present work validates the combination of drugs as an effective alternative to potentiate the action of anti-Leishmania agents and points to the quinoline compounds studied here as possible leishmanicidal drugs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available