7-Chloroquinolinotriazoles: synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies.
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.
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.
Guilherme R
GR
Pereira
Faculdade de Farmácia, UFOP, Rua Costa Sena 171, CEP 35400-000 Ouro Preto, MG, Brazil.
Geraldo Célio
GC
Brandão
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.
Lucas M
LM
Arantes
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.
Háliton A
HA
de Oliveira
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.
Renata Cristina
RC
de Paula
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.
Maria Fernanda A
MF
do Nascimento
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.
Fábio M
FM
dos Santos
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.
Ramon K
RK
da Rocha
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.
Júlio César D
JC
Lopes
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.
Alaíde Braga
AB
de Oliveira
D000480:Alkynes / Q000737:chemistry*; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001386:Azides / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D061565:Cycloaddition Reaction; D004351:Drug Resistance; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
D000480:Alkynes; D000962:Antimalarials; D001386:Azides; D014230:Triazoles
7-Chloroquinolinotriazoles; Antimalarial activity; Click chemistry; Cytotoxicity in HepG2; Plasmodium falciparum; Quinolines; Triazoles