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Antileishmanial Thioureas: Synthesis, Biological Activity and in Silico Evaluations of New Promising Derivatives.

  • Viana, Gil Mendes1
  • Soares, Deivid Costa2
  • Santana, Marcos Vinicius3
  • do Amaral, Lilian Henriques1
  • Meireles, Paloma Wetler1
  • Nunes, Raquel Pinto1
  • da Silva, Luiz Cláudio Rodrigues Pereira...1
  • Aguiar, Lúcia Cruz de Sequeira4
  • Rodrigues, Carlos Rangel5
  • de Sousa, Valeria Pereira1
  • Castro, Helena Carla3
  • Abreu, Paula Alvarez6
  • Sathler, Plínio Cunha1
  • Saraiva, Elvira Maria2
  • Cabral, Lucio Mendes1
  • 1 Universidade Federal do Rio de Janeiro, LabTIF, Faculdade de Farmácia, Ilha do Fundão.
  • 2 Universidade Federal do Rio de Janeiro, Laboratório de Imunobiologia das Leishmanioses, Instituto de Microbiologia Paulo de Góes.
  • 3 Universidade Federal Fluminense, LABiEMol, Departamento de Biologia Celular e Molecular, Outeiro de São João Baptista.
  • 4 Universidade Federal do Rio de Janeiro, Instituto de Química, Ilha do Fundão.
  • 5 Universidade Federal do Rio de Janeiro, ModMolQSAR, Faculdade de Farmácia, Ilha do Fundão.
  • 6 Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas, LaMCiFar. Universidade Federal do Rio de Janeiro-Campus Macaé.
Published Article
Chemical and Pharmaceutical Bulletin
Pharmaceutical Society of Japan
Publication Date
Jan 01, 2017
DOI: 10.1248/cpb.c17-00293
PMID: 28966275


Leishmaniasis is a neglected tropical disease caused by protozoan parasites belonging to the genus Leishmania. Currently, the drugs available for treatment of this disease present high toxicity, along with development of parasite resistance. In order to overcome these problems, efforts have been made to search for new and more effective leishmanicidal drugs. The aim of this study was to synthesize and investigate the leishmanicidal effect of N,N'-disubstituted thioureas against Leishmania amazonensis, with evaluation of their in silico pharmacokinetics and toxicity profiles. Our results showed that different thioureas could be obtained in high to moderate yields using simple reaction conditions. Nine thiourea derivatives (3e, 3i, 3k, 3l, 3p, 3q, 3v, 3x and 3z) were active against parasite promastigotes (IC50 21.48-189.10 µM), with low cytotoxicity on mice peritoneal macrophages (CC50>200 µM), except for thiourea 3e (CC50=49.22 µM). After that, the most promising thioureas (3k, 3l, 3p, 3q and 3v) showed IC50 ranging from 70 to 150 µM against L. amazonensis amastigotes in infected macrophages. Except for thiourea 3p, the leishmanicidal activity of the derivatives were independent of nitric oxide (NO) production. Thioureas 3q and 3v affected promastigotes cell cycle without disturbing the mitochondrial membrane potential. Furthermore, our derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. These data indicate that thiourea derivatives are good candidates as leading compounds for the development of new leishmanicidal drugs.

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