SAR Analysis, Mode of Action and In Vivo Studies

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.

Authors

Publication Details

Journal
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Published
2025-10-23
Primary Topic
Marine Sponges and Natural Products
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

SAR Analysis, Mode of Action and In Vivo Studies

Marcelo Yudi Icimoto, Wellington da Silva, Vinícius Bonatto, Sarah El Chamy Maluf et al.
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Marine Sponges and Natural Products
article

SAR Analysis, Mode of Action and In Vivo Studies

Marcelo Yudi Icimoto, Wellington da Silva, Vinícius Bonatto, Sarah El Chamy Maluf, Anna Caroline Campos Aguiar, Irene Layane de Sousa, Yasmin Annunciato, Marcos L. Gazarini, Gustavo Capatti Cassiano, Tania Valdés, Rafael V. C. Guido, Sofia Santana, Silvana A. Rocco, Giovana Rossi Mendes, Fabio Cardoso Cruz, Caio S. Moura, Renan Marcel Giampauli, Camila S. Barbosa, Carolina B G Teles, Gilberto Gaspar Duarte Ortin, Igor M. R. Moura, Priscilla Dantas de Souza Ventura, Miguel Prudêncio, Patricia Santos Barbosa, Carlos Roque Duarte Correia, Dhelio B. Pereira, Guilherme Eduardo Souza, Barbara dos Santos Rossetto, Amália dos Santos Ferreira
article en

Abstract

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.

Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Life below water
Openalex Percentile: Top 27%
Marine Sponges and Natural Products
Open Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.