The chemotherapy of rodent malaria. XLVIII. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 1: Studies leading to the development of novel<i>cis</i>-fused cyclopenteno derivatives

Peters, W.; Robinson, B. L.; Rossier, Jean-Claude; Jefford, Charles W.

doi:10.1080/00034983.1993.11812733

Cited by 52 publications

(49 citation statements)

References 8 publications

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“…Among these cis-fused cyclopenteno-1,2,4-trioxanes, Fenozan B07 (33a) had the most promising activity profile and was chosen for further development. 76,[80][81][82][83] Notably, trioxane 33a is equally active whether administered s.c. or p.o., and is no less effective than 2a, the most active semisynthetic artemisinin. Like 1, 2a, and 2b, the potency of 33a varies less than 4-fold against a wide spectrum of drug-resistant P. falciparum parasites.…”

Section: 74mentioning

confidence: 99%

“…Unfortunately, none of these more polar trioxanes possessed any significant activity, but this outcome was not unforeseen considering that the prototype trioxane 39 was 18-fold less effective than 1 in vivo. 80,91 In trioxane 40, Rong and Wu 92 melded most of the structural elements of 1 in a cholestane-type steroid-trioxane hybrid structure. Using a key phootooxygenation reaction, 40 was obtained in five steps from methyl 3-oxocholest-4-en-6b-yl acetate.…”

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confidence: 99%

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Synthetic peroxides as antimalarials

Tang

Dong²,

Vennerstrom³

2004

Medicinal Research Reviews

259

123

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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 synthetic antimalarial peroxides have been prepared. Yet, identification of orally active synthetic peroxide drug development candidates that are easily synthesized, inexpensive, and with good biopharmaceutical properties has been surprisingly difficult. In this review, we document the pitfalls and progress made in this endeavor. For each of 15 synthetic peroxide structural classes, we note highlights of the synthetic routes, product stereochemistry, and origin of the peroxide O atoms. Both in vitro and in vivo antimalarial data are then discussed and any SAR noted. Available data indicates that several synthetic 1,2,4-trioxanes are only marginally less effective than the semisynthetic artemisinins. Within a given peroxide chemical family, the more lipophilic members are more potent and possess better oral antimalarial activity in animal models than their more polar counterparts. This poses a challenge to identify peroxide structures with suitable "drug-like" physicochemical properties. Nonetheless, substantial progress has been made in the identification of a new generation of synthetic antimalarial peroxides.

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Section: 74mentioning

confidence: 99%

mentioning

confidence: 99%

Synthetic peroxides as antimalarials

Tang

Dong²,

Vennerstrom³

2004

Medicinal Research Reviews

259

123

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“…A modified Peter's 4-day suppressive test against P. berghei infection in mice was employed (Peters et al, 1993). Healthy Wistar mice (30-35 g) of both sexes divided into three groups of five mice per group was used for the study.…”

Section: In Vivo Pharmacodynamic Studiesmentioning

confidence: 99%

Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids

et al. 2014

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Contexts: Artemisinins and its derivatives are considered the basis in the treatment of Plasmodium falciparum malaria due to their high potency and rapid action. However, they have short half life, low solubility, and poor oral bioavailability, hence the need to formulate sustained release lipid particulate dosage form of these drugs. Objectives: To formulate and evaluate artesunate-loaded solid lipid microparticles (SLMs) based on structured lipid matrices consisting of soybean oil and dika wax. Materials and methods: The lipid matrices were characterized by differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD), and wide-angle X-ray diffraction (WAXD). The SLMs were prepared by hot melt-homogenization. Time-dependent particle size analysis, time-dependent pH stability studies, encapsulation efficiency (EE%), and in vitro drug release were carried out on the SLMs. In vivo anti-malarial studies were performed using a modified Peter's 4-day suppressive protocol using Plasmodium berghei infected mice. Results and discussion: Thermograms of the lipid matrices showed modifications in the microstructure of dika wax as a result of inclusion of soybean oil. SAXD and WAXD diffractograms showed that the lipid matrices were found to be non-lamellar. Particle size of SLM increased with time, while the pH was almost constant. The SLMs had maximum EE% of 80.6% and sustained the release of artesunate more than the reference tablet. In vivo pharmacodynamic studies showed that the SLMs had significant (p50.05) reduction in parasitaemia compared with reference tablet. Conclusion: Artesunate-loaded SLMs could be used once daily in the treatment of malaria.

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“…10 7 infected erythrocytes on day 0. The treatment dose was given 3 h after infection on day 0 and was repeated once daily for 3 days, as a 4-day-blood schizonticidal test [3] . Two modes of administration of the treatment (intraperitoneal and oral route) were studied.…”

Section: P Falciparum In Vitro Culture and Antiplasmodial Activitymentioning

confidence: 99%

In vitro and in vivo Antiplasmodial Activity of <i>Momordica balsamina</i> Alone or in a Traditional Mixture

et al. 2006

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Background: Because of the dramatic situation of malaria in Africa, there is an urgent need to find new and cheap drugs, such as herbal medicines. Here we report the study of the in vitro and in vivo antimalarial activity of Momordica balsamina alone or in a traditional mixture used in Niger. Methods: Extracts were obtained with different solvents and tested in vitro on Plasmodium falciparum and in vivo on Plasmodium vinckei. Results: The best extracts are methanolic and present promising results in vivo by intraperitoneal and oral administration. Conclusion: The antimalarial activity of M. balsamina, traditionally used in Niger, is confirmed in vitro and in vivo without any toxicity in healthy mice.

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The chemotherapy of rodent malaria. XLVIII. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 1: Studies leading to the development of novelcis-fused cyclopenteno derivatives

Cited by 52 publications

References 8 publications

Synthetic peroxides as antimalarials

Synthetic peroxides as antimalarials

Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids

In vitro and in vivo Antiplasmodial Activity of <i>Momordica balsamina</i> Alone or in a Traditional Mixture

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