2 research outputs found
Synthesis and Structure–Activity Relationships of the Novel Antimalarials 5‑Pyridinyl-4(1<i>H</i>)‑Pyridones
Malaria
is still one of the most prevalent parasitic infections
in the world, with half of the world’s population at risk for
malaria. The effectiveness of current antimalarial therapies, even
that of the most recent class of antimalarial drugs (artemisinin-combination
therapies, ACTs), is under continuous threat by the spread of resistant <i>Plasmodium</i> strains. As a consequence, there is still an
urgent requirement for new antimalarial drugs. We previously reported
the identification of 4(1<i>H</i>)-pyridones as a novel
series with potent antimalarial activities. The low solubility was
identified as an issue to address. In this paper, we describe the
synthesis and biological evaluation of 4(1<i>H</i>)-pyridones
with potent antimalarial activities in vitro and in vivo and improved
pharmacokinetic profiles. Their main structural novelties are the
presence of polar moieties, such as hydroxyl groups, and the replacement
of the lipophilic phenyl rings with pyridines on their lipophilic
side chains
Case Study of Small Molecules As Antimalarials: 2‑Amino-1-phenylethanol (APE) Derivatives
Antiparasitic oral drugs have been
associated to lipophilic molecules
due to their intrinsic permeability. However, these kind of molecules
are associated to numerous adverse effects, which have been extensively
studied. Within the Tres Cantos Antimalarial Set (TCAMS) we have identified
two small, soluble and simple hits that even presenting antiplasmodial
activities in the range of 0.4–0.5 μM are able to show
in vivo activity