Description | [a] C. de Souza Pereira, V. Schmitz, Prof. H. F. Dos Santos, Prof. M. Navarro
Departamento de Química
Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer, s/n –
Campus Universitário, Bairro Martelos CEP 36036-900, Juiz de Fora, Minas
Gerais (Brasil)
E-mail: maribel.navarro@ufjf.edu.br
[b] H. Costa Quadros, Dr. D. R. Magalhaes Moreira,
R. I. Santos De Deus Da Silva, Dr. M. Botelho Pereira Soares
Instituto Gonçalo Moniz
Fundação Oswaldo Cruz, Av. Waldemar Falcão, 121, Candeal, Salvador,
Bahia (Brasil)
[c] Dr. W. Castro
Centro de Química
Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de
Química, Carretera Panamericana, Km 11, Altos de Pipe, San Antonio de los
Altos Miranda, 1020-A, Caracas (Venezuela)
[d] Dr. D. Fontinha, Dr. M. Prudêncio
Instituto de Medicina Molecular João Lobo Antunes
Faculdade de Medicina, Universidade de Lisboa
<Lisboa (Portugal)
[e] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines
Unité Parasitologie et entomologie, Institut de recherche biomédicale des
armées, 19–21 Bd Jean Moulin, 13005 Marseille (France)
[f] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines
Aix-Marseille Univ, IRD, SSA, AP-HM, VITROME, 19–21 Bd Jean Moulin,
13005 Marseille (France)
[g] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines
IHU Méditerranée Infection, 19–21 Bd Jean Moulin, 13005 Marseille (France)
[h] I. Fonta, J. Mosnier, Dr. B. Pradines
Centre National de Référence du Paludisme, 19–21 Bd Jean Moulin, 13005
Marseille (France) | pt_BR |
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 | pt_BR |