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Parasitology Research

, Volume 117, Issue 11, pp 3585–3590 | Cite as

In vivo and in vitro antimalarial effect and toxicological evaluation of the chloroquine analogue PQUI08001/06

  • Patricia Alves Reis
  • Karla Ceodaro Pais
  • Monica Farah Pereira
  • Bruno Douradinha
  • Natália Ferreira Costa
  • Carlos Roland Kaiser
  • Patricia Torres Bozza
  • André Luiz Lisboa Areas
  • Mariano Gustavo Zalis
  • Marcelle de Lima Ferreira
  • Marcos Vinícius Nora de Souza
  • Valber da Silva Frutuoso
  • Hugo Caire de Castro-Faria-Neto
Original Paper

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.

Keywords

Malaria Plasmodium Antimalarial drug Chloroquine Chloroquine resistance 

Notes

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.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.

Supplementary material

436_2018_6057_Fig4_ESM.png (67 kb)
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)

436_2018_6057_MOESM1_ESM.tiff (4 mb)
High Resolution Image (TIFF 4089 kb)
436_2018_6057_MOESM2_ESM.pptx (62 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)
436_2018_6057_MOESM3_ESM.docx (16 kb)
Table S1 (DOCX 15 kb)
436_2018_6057_MOESM4_ESM.docx (13 kb)
Table S2 (DOCX 12 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Patricia Alves Reis
    • 1
  • Karla Ceodaro Pais
    • 2
    • 3
  • Monica Farah Pereira
    • 1
  • Bruno Douradinha
    • 4
  • Natália Ferreira Costa
    • 2
  • Carlos Roland Kaiser
    • 3
  • Patricia Torres Bozza
    • 1
  • André Luiz Lisboa Areas
    • 5
  • Mariano Gustavo Zalis
    • 5
  • Marcelle de Lima Ferreira
    • 2
    • 3
  • Marcos Vinícius Nora de Souza
    • 2
  • Valber da Silva Frutuoso
    • 1
  • Hugo Caire de Castro-Faria-Neto
    • 1
  1. 1.Laboratório de ImunofarmacologiaInstituto Oswaldo CruzManguinhosBrazil
  2. 2.Instituto de Tecnologia em Fármacos (Farmanguinhos), Fundação Oswaldo CruzManguinhosBrazil
  3. 3.Instituto de Química, Laboratório de Ressonância Magnética NuclearRio de JaneiroBrazil
  4. 4.Unità di Medicina Rigenerativa e Immunologia, Fondazione Ri.MED c/o IRCCS-ISMETTPalermoItaly
  5. 5.Laboratorio de Infectologia e Parasitologia Molecular, Serviço de Patologia ClínicaHospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de JaneiroRio de JaneiroBrazil

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