2. Academic Validation
  3. 7-Chloroquinolinotriazoles: synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies

7-Chloroquinolinotriazoles: synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies

  • Eur J Med Chem. 2014 Feb 12:73:295-309. doi: 10.1016/j.ejmech.2013.11.022.
Guilherme R Pereira 1,  Geraldo Célio Brandão 2,  Lucas M Arantes 3,  Háliton A de Oliveira Jr 1,  Renata Cristina de Paula 1,  Maria Fernanda A do Nascimento 1,  Fábio M dos Santos 4,  Ramon K da Rocha 3,  Júlio César D Lopes 3,  Alaíde Braga de Oliveira 5
Affiliations

Affiliations

  • 1 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
  • 2 Faculdade de Farmácia, UFOP, Rua Costa Sena 171, CEP 35400-000 Ouro Preto, MG, Brazil.
  • 3 Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
  • 4 Programa de Pós-Graduação em Bioinformática, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
  • 5 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil. Electronic address: alaidebraga@terra.com.br.
PMID: 24469080 DOI: 10.1016/j.ejmech.2013.11.022
Abstract

Twenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) Click Chemistry between 4-azido-7-chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 μM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 μM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained.

Keywords

7-Chloroquinolinotriazoles; Antimalarial activity; Click chemistry; Cytotoxicity in HepG2; Plasmodium falciparum; Quinolines; Triazoles.

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