Antimalarials based on the dioxane scaffold of plakortin. A concise synthesis and SAR studies.

  title={Antimalarials based on the dioxane scaffold of plakortin. A concise synthesis and SAR studies.},
  author={Caterina Fattorusso and Marco Giovanni Persico and Nicoletta Basilico and Donatella Taramelli and Ernesto Fattorusso and Fernando Scala and Orazio Taglialatela‐Scafati},
  journal={Bioorganic \& medicinal chemistry},
  volume={19 1},
Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity
Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic
A new class of antimalarial dioxanes obtained through a simple two-step synthetic approach: rational design and structure-activity relationship studies.
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.
Regioselective synthesis and antibacterial evaluation of novel bis-pyrimidine derivatives via a three-component reaction
A series of novel bis-2-phenylpyrimidines with alkyl linkages have been prepared by a three-component cyclo-condensation of benzamidine hydrochloride, β-ketoester, and dihaloalkanes. The easy work-up
Optimized Synthesis and Antimalarial Activity of 1,2‐Dioxane‐4‐carboxamides
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.
Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin.
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.
The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism
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 derivatives from marine organisms: 1,2-dioxanes of the plakortin family as novel antimalarial agents.
Results obtained confirmed the crucial role of the cycloperoxide functionality, and revealed other structural features critical for antimalarial activity, namely the "Western" alkyl side chain, the dioxane ring conformation, and the absolute configuration of the stereogenic carbons on the 1,2-doxane ring, when affecting the bioactive ring conformed.
Antimalarial Polyketide Cycloperoxides from the Marine SpongePlakortis simplex
Three new (5–7) and two known (4 and 8) polyketide derivatives have been isolated from the Caribbean sponge Plakortis simplex. Their stereostructures have been determined by spectroscopic methods and
Insight into the mechanism of action of plakortins, simple 1,2-dioxane antimalarials.
The 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 radical, followed by rearrangement to give a carbon radical centered on the "western" alkyl side-chain.
1,2,4-Trioxanes as potential antimalarial agents.
A number of 1,2,4-trioxanes were prepared and tested for antimalarial activity in search of a simplified analogue of the naturally occurring antimalaria qinghaosu, which showed an IC50 of 1 ng/mL for both strains.
Manadoperoxides A-D from the Indonesian sponge Plakortis cfr. simplex. Further insights on the structure-activity relationships of simple 1,2-dioxane antimalarials.
The new endoperoxyketal polyketides manadoperoxides A-D (2-5) have been isolated from the Indonesian sponge Plakortis cfr. simplex and their stereostructures established by means of spectroscopic
Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action.
Experiments with ferrous reagents indicate that active peroxides including 14 and its congeners kill the parasite by alkylation with a sterically non-encumbered C-centered radical, however, another possibility is the involvement of a Fe(IV)=O species as the toxic agent.
Activity against Plasmodium falciparum of cycloperoxide compounds obtained from the sponge Plakortis simplex.
Evaluated in vitro the antimalarial activity of the major cycloperoxides extracted from the sponge Plakortis simplex, and the activity of plakortin and dihydroplakortsin was significantly higher against chloroquine-resistant than chloroquin-susceptible parasites, following a pattern similar to that of artemisinin, although they were 50-fold less active.
Osmium catalyzed dihydroxylation of 1,2-dioxines: a new entry for stereoselective sugar synthesis.
Preliminary work on the catalytic asymmetric ring-opening of meso-peroxy diols using the Co(II) Jacobsens's catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines is possible.
Concise preparation of the (3E,5Z)-alkadienyl system. New approach to the synthesis of principal insect sex pheromone constituents.
A new rapid and low-cost preparation of the (3E,5Z)-3,5-alkadienyl system was developed, encountered in several insect pheromone constituents, and constituted synthetic targets of considerable interest for the semiochemical community.