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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)
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)
In this paper, we propose an analytical approach to predict the performance of web service composition built on BPEL. The approach first translates web service composition specification into Stochastic Petri Nets. From the SPN model and its corresponding continuous-time Markov chain, we derive the analytical performance estimates of process-completion-time.(More)
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 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)
This paper describes the discovery of synthetic 1,2,4-trioxolane antimalarials and how we established a workable structure-activity relationship in the context of physicochemical, biopharmaceutical, and toxicological profiling. An achiral dispiro-1,2,4-trioxolane (3) in which the trioxolane is flanked by a spiroadamantane and spirocyclohexane was rapidly(More)
Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16-tetraoxadispiro[5.2.5.2]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)
OBJECTIVES The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane (OZ78) were determined both in vivo and in vitro. METHODS Two weeks post-infection Echinostoma caproni-infected mice were administered single oral doses of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with 50-400 mg/kg OZ78 3 and 8-9 weeks(More)
Triclabendazole is the drug of choice against Fasciola hepatica infections in humans and animals. However, parasite resistance against triclabendazole is spreading in the veterinary field, and there are no drugs of comparable activity currently available for the treatment and control of fascioliasis. We investigated the efficacy of single oral doses of(More)
Because the synthetic trioxolane OZ78 is active against the liver fluke Fasciola hepatica, we were motivated to investigate the in vivo and in vitro activity against another liver fluke, namely Clonorchis sinensis. Rats infected with C. sinensis for 2 and 5 wk were treated orally with single doses of OZ78 (75, 150, or 300 mg/kg). Worm burden reductions were(More)