Fluorescent Marinoquinoline Derivative as Inhibitors of <i>Plasmodium falciparum</i>: SAR Analysis, Mode of Action and In Vivo Studies.

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 (IC₅₀^3D7 = 0.28 μM; CC₅₀^HepG2 = 53 μM), ex vivo (EC₅₀^Pf = 1.2 μM; EC₅₀^Pv = 0.53 μM), in vivo (3 × 50 mg/kg oral dose resulted in a 96% reduction in parasitemia in Plasmodium berghei-infected mice), physicochemical (Sol_7.4 = 171 μM; LogD_7.4 = 3.9), and pharmacokinetic (P_app = 9.4 × 10^-6 cm/s, human Cl

SUBMITTER: Santos Barbosa P 

PROVIDER: S-EPMC12557366 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature