Related Experiment Video
Updated: Aug 7, 2026
07:56
Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron
Published on: August 12, 2019
Tetraoxane antimalarials and their reaction with Fe(II)
Igor Opsenica1, Natasa Terzić, Dejan Opsenica
1Institute of Chemistry, Technology and Metallurgy, Belgrade, Serbia and Montenegro.
Journal of Medicinal Chemistry
|June 23, 2006
Summary
New tetraoxane compounds show potent antimalarial activity against resistant Plasmodium falciparum strains. These compounds are metabolically stable and demonstrate efficacy in vivo, offering a promising alternative to existing treatments.
Area of Science:
- Medicinal Chemistry
- Parasitology
- Drug Discovery
Background:
- Artemisinin and its derivatives are crucial antimalarial drugs.
- Emergence of drug-resistant Plasmodium falciparum strains necessitates novel therapeutic agents.
- The mechanism of action of tetraoxane antimalarials, particularly the role of radical species, requires further elucidation.
Purpose of the Study:
- To synthesize and evaluate novel mixed tetraoxanes derived from cholic acid and 4-oxocyclohexanecarboxylic acid for antimalarial activity.
- To assess the metabolic stability and in vivo efficacy of promising tetraoxane candidates.
- To investigate the mechanism of action, specifically the radical species involved in tetraoxane-mediated parasite death.
Main Methods:
- Synthesis of mixed tetraoxanes from cholic acid and 4-oxocyclohexanecarboxylic acid.
- In vitro testing against chloroquine-susceptible and resistant Plasmodium falciparum strains (IC50, IC90).
- In vitro metabolism studies to assess metabolic stability.
- In vivo efficacy studies in mouse models.
- Electron Paramagnetic Resonance (EPR) experiments to detect radical species during Fe(II)-induced scission.
Main Results:
- Synthesized tetraoxanes 5a and 13 exhibited activity comparable to artemisinin against various Plasmodium falciparum strains.
- Compound 13 demonstrated metabolic stability in vitro.
- Compound 15 showed significant in vivo efficacy in mice at multiple dosages with no observed toxic effects.
- Tetraoxane 19 displayed potent antiproliferative activity (LC50 of 17 nM) with a high maximum tolerated dose.
- EPR studies detected RO* radicals, suggesting their role in parasite death, potentially challenging the established role of C radicals.
Conclusions:
- Novel tetraoxanes possess significant antimalarial and antiproliferative properties.
- Metabolic stability and in vivo efficacy highlight the therapeutic potential of these compounds.
- The mechanism of action may involve RO* radicals, broadening the understanding of peroxide prodrug antimalarial activity.
More Related Videos
09:51TD-DFT Guided Advanced E-Eye Sensing Technique for On-site Quantification of Fe, Cr, F, and As in the Environmental, Biological, and Food Samples
Published on: September 19, 2025
06:34Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
Related Concept Videos
01:21Antiprotozoal 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...
01:19Masking and Demasking Agents
EDTA titrations may necessitate masking and demasking agents to temporarily protect a particular metal ion in a mixture from the EDTA reaction. These agents facilitate the sequential analysis of the metal ions by forming stable complexes with some—but not all—metal ions during certain steps.
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on the metal...
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on the metal...
01:26Redox Titration: Other Oxidizing and Reducing Agents
Besides iodine, other oxidizing or reducing agents can serve as titrants in redox titrations. Common oxidizing titrants include KMnO4, cerium(IV), and K2Cr2O7. The choice of oxidizing titrants depends on factors like stability, cost, analyte strength, and reaction rate between the analyte and titrant. KMnO4 is a strong oxidizing titrant that reduces from Mn(VII) to Mn(II) in a highly acidic solution, simultaneously oxidizing the analyte to a higher oxidation state. In this case, KMnO4 acts as a...
02:58Properties of Transition Metals
Transition metals are defined as those elements that have partially filled d orbitals. As shown in Figure 1, the d-block elements in groups 3–12 are transition elements. The f-block elements, also called inner transition metals (the lanthanides and actinides), also meet this criterion because the d orbital is partially occupied before the f orbitals.
01:26EDTA: Auxiliary Complexing Reagents
EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
01:17Oxidation of Phenols to Quinones
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...