Abstract
Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant and -sensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.
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Acknowledgements
We thank the anonymous reviewers for their comments, suggestions, and input which rendered this work more accurate and accessible to the readers. We are grateful to Dr. Erika Martins Braga and Juliana Carvalho Tavares for kindly providing P. berghei strain NK65. The authors are grateful to Dr. Claudio Tadeu Daniel-Ribeiro for kindly providing the P. falciparum strains 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant).
Funding
We thank the following funding agencies for the financial support: CNPq, FAPERJ, PRONEX, PAPES, and Fondazione Ri.MED.
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Section Editor: Kevin S.W. Tan
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Fig. S1
Synthetic route for preparation of PQUI08001/06. From 4,7-dichloroquinoline (left), the derivative 2-[(7-chloro-4-quinoliny)amino] ethanol (compound 1) which, per turn, originated the derivative N-(2-chloroethyl)-N-(7-chloro-4-quinolinyl) amine (compound 2). From the latter, PQUI08001/06 (right) was obtained. (PNG 67 kb)
Fig. S2
Survival curves analysis during P. berghei ANKA 4-day (A) showed a significant difference at chloroquine 25 mg/kg and Rane (established infection) test (B) showed significant difference among chloroquine and PQUI08001 25, 50 and 100 mg/kg in relation to vehicle group and no significant difference chloroquine and PQUI08001. Chloroquine and PQUI08001/06 concentrations are indicated in the graph. Curves were evaluated by Log-rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests. * p < 0.05 or less in relation to vehicle group. (PPTX 61 kb)
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Reis, P.A., Pais, K.C., Pereira, M.F. et al. In vivo and in vitro antimalarial effect and toxicological evaluation of the chloroquine analogue PQUI08001/06. Parasitol Res 117, 3585–3590 (2018). https://doi.org/10.1007/s00436-018-6057-6
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DOI: https://doi.org/10.1007/s00436-018-6057-6