Yuxiang Dong

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Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the(More)
The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive(More)
Schistosomiasis is a parasitic disease that remains of considerable public health significance in tropical and subtropical environments. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we present new data on the antischistosomal properties of representative synthetic(More)
BACKGROUND AND PURPOSE Perivascular adipose tissue (PVAT) releases adipocyte-derived hyperpolarizing factors (ADHFs) that may partly act by opening myocyte K(+) channels. The present study in rat and mouse mesenteric arteries aimed to identify the myocyte K(+) channel activated by PVAT and to determine whether adiponectin contributed to the hyperpolarizing(More)
Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16-tetraoxadispiro[]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone(More)
The discovery of artemisinin in 1971 initiated a new era in antimalarial chemotherapy. Although the clinically useful semisynthetic artemisinin derivatives are rapid acting and potent antimalarial drugs, they have short half-lives and must be administered over a period of 5-7 days, leading to noncompliance and recrudescence. With this in view, many(More)
An unsaturated dispiro 1,2,4,5-tetraoxane formed by peroxidation of (+)-dihydrocarvone was converted into four structurally diverse derivatives. X-ray crystallographic analysis shows that the structures possess central tetraoxane rings with spiro-2,5-disubstituted cyclohexylidene substituents and 6-membered rings in classical chair conformations. As(More)
Peroxidic antimalarials such as the semisynthetic artemisinins are critically important in the treatment of drug-resistant malaria. Nevertheless, their peroxide bond-dependent mode of action is still not well understood. Using combination experiments with cultured Plasmodium falciparum cells, we investigated the interactions of the nitroxide radical spin(More)
* To whom correspondence should be addressed: Susan Charman, Centre for Drug 19 Candidate Optimisation, Victorian College of Pharmacy, Monash University, 20 381 Royal Parade, Parkville, Victoria 3052, Australia. Tel: +61 3 9903 9626; Fax: 21 +61 3 9903 9560; email: susan.charman@vcp.monash.edu.au 22 23 24 AC CE TE D Copyright © 2008, American Society for(More)
The reaction of spiro- and dispiro-1,2,4-trioxolane antimalarials with heme has been investigated to provide further insight into the mechanism of action for this important class of antimalarials. A series of trioxolanes with various antimalarial potencies was found to be unreactive in the presence of Fe(III) hemin, but all were rapidly degraded by reduced(More)