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Related Concept Videos

Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
Modified-Release Drug Delivery Systems: Influencing Factors01:20

Modified-Release Drug Delivery Systems: Influencing Factors

Modified-release drug delivery systems are designed to optimize the therapeutic effect of drugs by minimizing side effects, reducing the dosage required, and controlling drug release to align with pharmacokinetic and pharmacodynamic needs. The system depends on two key factors: the drug's release from the formulation and its movement through the body to the target site. Unlike conventional dosage forms, where absorption is the limiting step, the rate of drug release is the key determinant in...
Modified-Release Drug Delivery Systems: Stimuli-Activated01:30

Modified-Release Drug Delivery Systems: Stimuli-Activated

Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also called...
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Anthelminthic Agents

Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
Extraction: Advanced Methods00:56

Extraction: Advanced Methods

Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is formed in...
Modified-Release Drug Delivery Systems: Rate-Programmed II01:19

Modified-Release Drug Delivery Systems: Rate-Programmed II

Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...

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Ookluc: A Plasmodium berghei Line for Identifying Transmission-blocking Compounds
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Metal-Drug Complexes as Long-Release Application for Antimalarial PfFNT-Inhibitors.

Finn Tiedjens1, Björn Henke1, Ulrich Girreser1

  • 1Department of Pharmaceutical and Medicinal Chemistry, Kiel University, Kiel, Germany.

Chemmedchem
|July 1, 2026
PubMed
Summary

Developing long-acting antimalarial drugs is crucial. Metal complexes of Plasmodium falciparum formate-nitrite transporter (PfFNT) inhibitors show sustained drug release, offering potential for long-acting depot formulations against malaria.

Keywords:
PfFNTchemopreventioninhibitormalariametal–drug complex

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Area of Science:

  • Medicinal Chemistry
  • Parasitology
  • Drug Delivery

Background:

  • Inhibiting the Plasmodium falciparum formate-nitrite transporter (PfFNT) is a promising antimalarial strategy.
  • PfFNT inhibitors are potent against blood-stage parasites and effective in vivo.
  • Activity against liver-stage parasites suggests chemopreventive potential.

Purpose of the Study:

  • To explore metal complexes of PfFNT inhibitors for long-acting depot formulations.
  • To investigate sustained drug release kinetics of these complexes.
  • To assess the potential for chemopreventive antimalarial applications.

Main Methods:

  • Formation and characterization of Mg2+, Ca2+, and Zn2+ complexes with a PfFNT inhibitor via vinylogous acid chelation.
  • Spectroscopic analysis of complex structure.
  • In vitro release studies using dialysis assays and simulated plasma concentration analysis.

Main Results:

  • Metal complexes formed amorphous particles with metal-dependent solubilities.
  • Sustained, near zero-order release of the PfFNT inhibitor was observed.
  • Zinc complexes exhibited low solubility and slow release kinetics, enabling sustained drug exposure.

Conclusions:

  • Coordination of vinylogous acid motifs with metal ions can create long-acting depot formulations.
  • This strategy holds promise for developing sustained-release anti-infective agents.
  • Further development could lead to improved antimalarial chemoprevention and treatment.