Insight into the mechanism of action of plakortins, simple 1,2-dioxane antimalarials.

@article{TaglialatelaScafati2010InsightIT,
  title={Insight into the mechanism of action of plakortins, simple 1,2-dioxane antimalarials.},
  author={Orazio Taglialatela‐Scafati and Ernesto Fattorusso and Adriana Romano and Fernando Scala and Vincenzo Barone and Paola Cimino and Emiliano Stendardo and Bruno Catalanotti and Marco Giovanni Persico and Caterina Fattorusso},
  journal={Organic \& biomolecular chemistry},
  year={2010},
  volume={8 4},
  pages={
          846-56
        }
}
A multidisciplinary approach, based on molecular dynamics/mechanics, ab initio calculations, dynamic docking studies, and chemical reactions, has been employed to gain insight into the mechanism of the antimalarial action of plakortin and dihydroplakortin, simple 1,2-dioxanes isolated from the sponge Plakortis simplex. Our results show that these molecules, after interaction of the endoperoxide bond with Fe(ii), likely coming from the heme molecule, give rise to the formation of an oxygen… 
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The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism
TLDR
Results indicate that the studied compounds produce reactive carbon radical species after being reductively activated by heme, similarly to artemisinin, which should represent the key event responsible for Plasmodium death.
Endoperoxide polyketides from a Chinese Plakortis simplex: further evidence of the impact of stereochemistry on antimalarial activity of simple 1,2-dioxanes.
Antimalarials based on the dioxane scaffold of plakortin. A concise synthesis and SAR studies.
Further optimization of plakortin pharmacophore: structurally simple 4-oxymethyl-1,2-dioxanes with promising antimalarial activity.
PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity.
Fifteen polyketides, including the first hydroxylated plakortone (12) and plakdiepoxide (15), the first polyketide to embed a vicinal diepoxide, have been isolated from the Chinese sponge Plakortis…
Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin.
TLDR
Interestingly, it appears that minor structural changes, such as a shift of the methyl group around the dioxane ring, can dramatically affect the antitrypanosomal activity.
Computer-Aided Drug Discovery from Marine Compounds: Identification of the Three-Dimensional Structural Features Responsible for Antimalarial Activity.
TLDR
An integrated computational approach has been employed to gain insight into the mechanism of action of new antimalarial agents characterized by the scaffold of the marine compounds plakortin and aplidinone, showing that these molecules, after interaction with Fe(II), give rise to the formation of radical species.
Optimized Synthesis and Antimalarial Activity of 1,2‐Dioxane‐4‐carboxamides
TLDR
An optimized two-step synthesis of 3 characterized by high yields, simple work-up procedures and high diastereoselectivity allowing us to readily prepare 3 on multigram scale is presented.
A new class of antimalarial dioxanes obtained through a simple two-step synthetic approach: rational design and structure-activity relationship studies.
TLDR
This study demonstrated that according to the hypothesized mechanism of action, the antimalarial activity can be improved through rational structural modifications, paving the way for the development of new simplified antimalaria endoperoxides.
Bridged bicyclic 2,3-dioxabicyclo[3.3.1]nonanes as antiplasmodial agents: Synthesis, structure-activity relationships and studies on their biomimetic reaction with Fe(II).
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References

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