Kristina Borstnik

Antimalarial chemotherapeutic peroxides: artemisinin, yingzhaosu A and related compounds.

Mechanism-based rational design and gram-scale chemical synthesis have produced some new trioxane and endoperoxide antimalarial drug candidates that are efficacious and safe. This review summarises recent achievements in this area of peroxide drug development for malaria chemotherapy.

Enantiomeric 1,2,4-Trioxanes Display Equivalent in vitro Antimalarial Activity Versus Plasmodium falciparum Malaria Parasites: Implications for the Molecular Mechanism of Action of the Artemisinins

The aim of this study was to synthesise pure enantiomers of potent antimalarial 1,2,4‐trioxanes, which are related to the natural antimalarial artemisinin, and then to assay each against a panel of Plasmodium falciparum strains. The working hypothesis was that if the artemisinin derivatives interact with a specific protein‐target site, then there should be stereoselective differences in their activity. In five different P. falciparum isolates, however, the trioxane enantiomers (+)‐7 a, (−)‐7 a and (+)‐7 b, (−)‐7 b, showed the same level of in vitro antiparasitic activity.

New chemical and biological aspects of artemisinin-derived trioxane dimers.

Joining two 10-deoxoartemisinin trioxane units via a p-diacetylbenzene linker produces new C-10 non-acetal dimers and. 1H NMR spectroscopy allows unambiguous assignment of the stereochemistry at C-10 in these dimers. Successful replacement of both carbonyl oxygen atoms in these diketone dimers by fluorine atoms produces new tetrafluorinated dimers and. Each dimer was evaluated in vitro for antimalarial, antiproliferative, and antitumor activities; ketone dimers and, more than fluorinated dimers and, are promising for chemotherapy of both malaria and cancer.

New silicon-mediated ring expansion of n-sized conjugated cycloalkenones into homoallylic n+3 lactones

Abstract Silicon nucleophilic β-addition to various 2-cycloalkenones, followed ultimately by mild and rapid α-alkylation of the corresponding cycloalkanone enolates using diverse epoxides and BF3·OEt2, produces useful γ-lactols and γ-hydroxyketones. Hypervalent iodine-promoted oxidative fragmentation then yields regiospecifically unsaturated, 3-atom ring expanded, 8–10 membered homoallylic lactones with good control of alkene geometry.

Malaria: new chemotherapeutic peroxide drugs.

Chemical insights into artemisinins biological mechanism of action have allowed rational design of some new trioxane and endoperoxide antimalarial drug candidates that are efficacious and safe. This review summarizes recent achievements in this area of peroxide drug development for malaria chemotherapy.