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https://www.arca.fiocruz.br/handle/icict/49041
A NOVEL HYBRID OF CHLOROQUINE AND PRIMAQUINE LINKED BY GOLD(I): MULTITARGET AND MULTIPHASE ANTIPLASMODIAL AGENT
Primaquina
Malaria
Plasmodium
Resistência a medicamnetos
Tratamento
Author
Pereira, Caroline de Souza
Quadros, Helenita Costa
Moreira, Diogo Rodrigo Magalhaes
Castro, William
Silva, Romulo Ivisson Santos de Deus da
Soares, Milena Botelho Pereira
Fontinha, Diana
Prudêncio, Miguel
Schmitz, Vinicius
Santos, Hélio F. dos
Gendrot, Mathieu
Fonta, Isabelle
Mosnier, Joel
Pradines, Bruno
Navarro, Maribel
Quadros, Helenita Costa
Moreira, Diogo Rodrigo Magalhaes
Castro, William
Silva, Romulo Ivisson Santos de Deus da
Soares, Milena Botelho Pereira
Fontinha, Diana
Prudêncio, Miguel
Schmitz, Vinicius
Santos, Hélio F. dos
Gendrot, Mathieu
Fonta, Isabelle
Mosnier, Joel
Pradines, Bruno
Navarro, Maribel
Affilliation
"Múltipla ver em Notas"
Abstract
Plasmodium parasites kill 435 000 people around the world
every year due to unavailable vaccines, a limited arsenal of
antimalarial drugs, delayed treatment, and the reduced clinical
effectiveness of current practices caused by drug resistance.
Therefore, there is an urgent need to discover and develop new
antiplasmodial candidates. In this work, we present a novel
strategy to develop a multitarget metallic hybrid antimalarial
agent with possible dual efficacy in both sexual and asexual
erythrocytic stages. A hybrid of antimalarial drugs (chloroquine
and primaquine) linked by gold(I) was synthesized and
characterized by spectroscopic and analytical techniques. The
CQPQ-gold(I) hybrid molecule affects essential parasite targets,
it inhibits β-hematin formation and interacts moderately with
the DNA minor groove. Its interaction with PfTrxR was also
examined in computational modeling studies. The CQPQ-gold(I)
hybrid displayed an excellent in vitro antimalarial activity
against the blood-stage of Plasmodium falciparum and liverstage
of Plasmodium berghei and efficacy in vivo against P.
berghei, thereby demonstrating its multiple-stage antiplasmodial
activity. This metallic hybrid is a promising chemotherapeutic
agent that could act in the treatment, prevention, and
transmission of malaria
Keywords in Portuguese
CloriquinaPrimaquina
Malaria
Plasmodium
Resistência a medicamnetos
Tratamento
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