New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.
Malaria continues to be an important public health problem in the world. Nowadays, the widespread parasite resistance to many drugs used in antimalarial therapy has made the effective treatment of cases and control of the disease a constant challenge. Therefore, the discovery of new molecules with good antimalarial activity and tolerance to human use can be really important in the further treatment of the disease. In this study we have investigated the antiplasmodial activity of 10 synthetic compounds derived from quinoline, five of them combined to sulfonamide and five to the hydrazine or hydrazide group. The compounds were evaluated according to their cytotoxicity against HepG2 and HeLa cell lines, their antimalarial activity against CQ-sensitive and CQ-resistant Plasmodium falciparum strains and, finally, their schizonticide blood action in mice infected with Plasmodium berghei NK65. The compounds exhibited no cytotoxic action in HepG2 and HeLa cell lines when tested up to a concentration of 100 μg/mL. In addition, the hydrazine or hydrazide derivative compounds were less cytotoxic against cell lines and more active against CQ-sensitive and CQ-resistant P. falciparum strains, showing high SI (>1000 when SI was calculated using the CC50 from the 3D7 strain as reference). When tested in vivo, the hydrazine derivative 1f compound showed activity against the development of blood parasites similar to that observed with CQ, the reference drug. Interestingly, the 1f compound demonstrated the best LipE value (4.84) among all those tested in vivo. Considering the in vitro and in vivo activities of the compounds studied here and the LipE values, we believe the 1f compound to be the most promising molecule for further studies in antimalarial chemotherapy.
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: bbtareis@hotmail.com.
Roberta Reis
RR
Soares
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: jmf_farm@yahoo.com.br.
José Marcio Fernandes
JM
da Silva
Instituto de Biotecnologia (IBTEC), Universidade Estadual Paulista, Alameda dos Tecomarias, s/n, 18607-440 Botucatu, SP, Brazil. Electronic address: biancabio@yahoo.com.br.
Bianca Cecheto
BC
Carlos
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: camilafonsecas@gmail.com.
Camila Campos
CC
da Fonseca
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: lailasouzabio@yahoo.com.br.
Laila Salomé Araújo
LS
de Souza
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: fernandavaleriolopes@hotmail.com.
Fernanda Valério
FV
Lopes
Instituto de Química de São Carlos, Universidade de São Paulo. Avenida João Dagnone, n° 1100, Jardim Santa Angelina, 13563-120 São Carlos, SP, Brazil. Electronic address: rafaelmafrapd@yahoo.com.br.
Rafael Mafra
RM
de Paula Dias
Núcleo de Pesquisa em Química Biológica (NQBio), Universidade de São João Del Rei, Rua Sebastião Gonçalves Coelho, Chanadour, 35501-296 Divinópolis, MG, Brazil. Electronic address: paulootaviomoreira@yahoo.com.br.
Paulo Otávio Lourenço
PO
Moreira
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: clarice.abramo@ufjf.edu.br.
Clarice
C
Abramo
Núcleo de Pesquisa em Química Biológica (NQBio), Universidade de São João Del Rei, Rua Sebastião Gonçalves Coelho, Chanadour, 35501-296 Divinópolis, MG, Brazil. Electronic address: viana@ufsj.edu.br.
Gustavo Henrique Ribeiro
GH
Viana
Núcleo de Pesquisa em Química Biológica (NQBio), Universidade de São João Del Rei, Rua Sebastião Gonçalves Coelho, Chanadour, 35501-296 Divinópolis, MG, Brazil. Electronic address: varotti@ufsj.edu.br.
Fernando
F
de Pila Varotti
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil. Electronic address: david.silva@ufjf.edu.br.
Adilson David
AD
da Silva
Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer s/n, Martelos, 36036-900 Juiz de Fora, MG, Brazil; Departamento of Global Health, University of South Florida, 3720 Spectrun Blvd, suit 304, Tampa, FL 33612, USA. Electronic address: kezia.scopel@ufjf.edu.br.
Kézia Katiani Gorza
KK
Scopel
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D015394:Molecular Structure; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*
D000962:Antimalarials; D011804:Quinolines
Antimalarial chemotherapy; Cytotoxicity; Malaria; Plasmodium falciparum; Quinoline derivatives