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Synthesis and anti-Plasmodium falciparum evaluation of novel pyrazolopyrimidine derivatives

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Abstract

Nine 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives with different substituents in the 4-position of the phenyl group and benzenesulfonamide moiety were synthesized and evaluated against Plasmodium falciparum. Six compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 5.13 to 12.22 µM. The most active derivative with substituents R1 = F / R2 = CH3 exhibited an IC50 value of 5.13 µM and an IS value of 62.90, which was higher than that of the control drug sulfadoxine. For this reason, it is possible to conclude that the 1H-pyrazolo[3,4-d]pyrimidine system is promising as a prototype for further studies of antimalarial candidates.

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Acknowledgements

We thank the Coordination of Improvement of Higher Education (CAPES) and the National Council of R&D of Brazil (CNPq) for the fellowships granted to the authors. We also thank the Foundation for Research of the State of Rio de Janeiro (FAPERJ), Technological Development Program on Products for Health (PDTIS), for financial support. LJMC, LCSP and NB are recipients of research productivity fellowships from the CNPq and from FAPERJ (“Cientista do Nosso Estado”).

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Authors and Affiliations

  1. Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos - FIOCRUZ, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ, 21041-250, Brazil

    Flávia F. Silveira, Lívia M. Feitosa, João C. M. Mafra, Maria de Lourdes G. Ferreira, Kamilla R. Rogerio, Nubia Boechat & Luiz C. S. Pinheiro

  2. Programa de Pós-Graduação em Química, PGQu Instituto de Química, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil

    Flávia F. Silveira, Lívia M. Feitosa, João C. M. Mafra & Kamilla R. Rogerio

  3. Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil

    Kamilla R. Rogerio & Leonardo J. M. Carvalho

Authors
  1. Flávia F. Silveira
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  2. Lívia M. Feitosa
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  3. João C. M. Mafra
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  4. Maria de Lourdes G. Ferreira
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  5. Kamilla R. Rogerio
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  6. Leonardo J. M. Carvalho
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  7. Nubia Boechat
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  8. Luiz C. S. Pinheiro
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Correspondence to Nubia Boechat or Luiz C. S. Pinheiro.

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Silveira, F.F., Feitosa, L.M., Mafra, J.C.M. et al. Synthesis and anti-Plasmodium falciparum evaluation of novel pyrazolopyrimidine derivatives. Med Chem Res 27, 1876–1884 (2018). https://doi.org/10.1007/s00044-018-2199-4

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  • DOI: https://doi.org/10.1007/s00044-018-2199-4

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