2. Academic Validation
  3. New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo

New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo

  • Bioorg Med Chem Lett. 2015 Jun 1;25(11):2308-13. doi: 10.1016/j.bmcl.2015.04.014.
Roberta Reis Soares 1,  José Marcio Fernandes da Silva 2,  Bianca Cecheto Carlos 3,  Camila Campos da Fonseca 4,  Laila Salomé Araújo de Souza 5,  Fernanda Valério Lopes 6,  Rafael Mafra de Paula Dias 7,  Paulo Otávio Lourenço Moreira 8,  Clarice Abramo 9,  Gustavo Henrique Ribeiro Viana 10,  Fernando de Pila Varotti 11,  Adilson David da Silva 12,  Kézia Katiani Gorza Scopel 13
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Instituto de Biotecnologia (IBTEC), Universidade Estadual Paulista, Alameda dos Tecomarias, s/n, 18607-440 Botucatu, SP, Brazil. Electronic address: biancabio@yahoo.com.br.
  • 4 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.
  • 5 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.
  • 6 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.
  • 7 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.
  • 8 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.
  • 9 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.
  • 10 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.
  • 11 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.
  • 12 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.
  • 13 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.
PMID: 25920564 DOI: 10.1016/j.bmcl.2015.04.014
Abstract

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.

Keywords

Antimalarial chemotherapy; Cytotoxicity; Malaria; Plasmodium falciparum; Quinoline derivatives.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z