Publicação

Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum

Ver documento

Detalhes bibliográficos
Resumo:We present insights into the mechanism of action of marinoquinolines (MQ), a novel class of lead candidates. Using a divergent synthetic approach, we developed a series of 20 new analogues with fluorescence properties. Structure–activity relationships analysis identified 19 as an attractive compound showing a combination of favorable in vitro (IC503D7= 0.28 μM; CC50HepG2= 53 μM), ex vivo (EC50Pf= 1.2 μM; EC50Pv= 0.53 μM), in vivo (3 × 50 mg/kg oral dose resulted in a 96% reduction in parasitemia in Plasmodium berghei-infected mice), physicochemical (Sol7.4= 171 μM; LogD7.4= 3.9), and pharmacokinetic (P_app = 9.4 × 10–6cm/s, human Clinthep,mic= 0.61–0.68 μL min–1mg–1) properties. Compound 19 selectively accumulates in infected erythrocytes, enters the digest vacuole and inhibits Plasmodium falciparum proteolytic activity, suggesting that MQs act as protease inhibitors. These findings strengthen the evidence that MQs are promising lead candidates for antimalarial drug discovery.
Autores principais:Santos Barbosa, Patricia
Outros Autores:Souza, Guilherme Eduardo; Maluf, Sarah El Chamy; Bonatto, Vinícius; Moura, Caio Silva; Mendes, Giovana Rossi; Valdes, Talita Alvarenga; Annunciato, Yasmin; Rossetto, Barbara dos Santos; Ventura, Priscilla Dantas de Souza; Ortin, Gilberto Gaspar Duarte; da Silva, Wellington; Icimoto, Marcelo Yudi; Ferreira, Amália dos Santos; Cruz, Fabio C.; Teles, Carolina B. G.; Pereira, Dhelio B.; Cassiano, Gustavo Capatti; Santana, Sofia; Prudêncio, Miguel; Barbosa, Camila S.; Moura, Igor M. R.; Giampauli, Renan Marcel; De Sousa, Irene Layane; Rocco, Silvana Aparecida; Gazarini, Marcos L.; Correia, Carlos Roque Duarte; Aguiar, Anna Caroline Campos; Guido, Rafael Victorio Carvalho
Assunto:Molecular Medicine Drug Discovery
Ano:2025
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL

Registos relacionados

Registos relacionados