Management of Toxoplasmosis

Georgiev, Vassil St.

doi:10.2165/00003495-199448020-00005

Cited by 75 publications

(32 citation statements)

References 38 publications

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“…Available medications for the prevention and treatment of toxoplasma infection show limited efficacy and have substantial side effects (5). Published studies have indicated that the naturally occurring 1,2,4-trioxane artemisinin and artemisinin derivatives such as artemether, originally developed for the treatment of malaria, have the ability to inhibit toxoplasma replication in vitro (2,4,6,10).…”

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confidence: 99%

“…While other antifolate compounds, such as pyrimethamine, have increased antitoxoplasma activity, their toxicity generally precludes widespread usage, particularly over prolonged periods of administration (5). The availability of low-toxicity compounds capable of the prevention and treatment of T. gondii in humans would represent a major advance in the treatment of infections in immunocompromised individuals.…”

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confidence: 99%

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In Vitro Inhibition of Toxoplasma gondii by Four New Derivatives of Artemisinin

Jones‐Brando

D’Angelo

Posner

et al. 2006

Antimicrob Agents Chemother

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Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is medically important and distributed worldwide. Currently available medications are limited in terms of efficacy and side effects. We synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of Toxoplasma gondii in cell culture.Toxoplasma gondii is an apicomplexan protozoan of worldwide medical importance. Humans are infected by T. gondii through contact with feces from infected cats, by the consumption of undercooked meat from infected animals, or by transmission from infected mother to fetus. This parasite can cause systemic infection and widespread organ damage in immunocompromised individuals and neonates. Infection of immunocompetent adults can result in fever and adenopathy (11). Serological studies indicate that T. gondii could be associated with chronic neuropsychiatric diseases or behavioral abnormalities in some populations (1,12).Available medications for the prevention and treatment of toxoplasma infection show limited efficacy and have substantial side effects (5). Published studies have indicated that the naturally occurring 1,2,4-trioxane artemisinin and artemisinin derivatives such as artemether, originally developed for the treatment of malaria, have the ability to inhibit toxoplasma replication in vitro (2, 4, 6, 10). While these trioxanes have a number of advantages in terms of rapid action and low levels of toxicity, they are limited in terms of absorption, bioavailability, and short half-life (i.e., easy hydrolysis into toxic dihydroartemisinin) (9). Thus, we have designed and synthesized five C-10 nonacetal, hydrolytically stable derivatives of artemisinin (8) and measured their ability to inhibit the replication of T. gondii in vitro.Artemisinin was obtained from Holley Pharmaceuticals Co., Inc., Fullerton, CA. Artemether was generously donated by Huiling Wang, University of Wuhan, China. Trimethoprim was purchased from Sigma Chemical Co. (St. Louis, MO). Chlorophenol red-␤-D-galactopyranoside (Roche, Indianapolis, IN), 100 mM in 100 mM HEPES (pH 7.2), was stored frozen at Ϫ80°C. CellTiter 96 AQ ueous One Solution Reagent for determining cytotoxicity was purchased from Promega Corp., Madison, WI.Structures of artemisinin and the derivatives are shown in Fig. 1. Trioxane C-10 primary alcohol 2a was prepared in 74% yield by hydroboration-oxidation of the corresponding known C-10 allyl trioxane. Esterification of primary alcohol 2a with benzoyl chloride led to benzoate ester 2b in 92% yield, and esterification with 2-bromobenzoyl chloride produced 2-bromobenzoate ester 2c in 86% yield. Deprotonation of the primary alcohol 2a using sodium hydride and then displacement of the bromide anion from citronelyl bromide gave citronelyl ether 2d in 55% yield. First, zinc-promoted deoxygenation of the known C-10 allyl trioxane and then hydroboration-oxidation produced dioxolane deoxy-2a in 72% yield. Each of these new lipid-soluble chromatographically purified artemisinin deriva...

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In Vitro Inhibition of Toxoplasma gondii by Four New Derivatives of Artemisinin

Jones‐Brando

D’Angelo

Posner

et al. 2006

Antimicrob Agents Chemother

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“…Newborns of women contracting toxoplasmosis during pregnancy should be treated with clindamycin to reduce the likelihood of developing late neurologic sequelae, including seizures. (Georgiev, 1994) …”

Section: Neurotoxoplasmosismentioning

confidence: 99%

Epilepsy Secondary to Parasitic Zoonoses of the Brain

Foyaca-Sibat¹

2011

Novel Aspects on Epilepsy

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“…However, these drugs cause adverse reactions, including the suppression of bone marrow, teratogenic effects in the first trimester of pregnancy, and sulfadiazine hypersensitivity [7]. Other drugs such as clindamycin, atovaquone, daspone, trimethoprim, pentamidine, and azithromycin have also been used, but side-effects such as diarrhoea, nausea, abdominal pain, cholestatic hepatitis, hepatomegaly, and hepatitis have been reported [8]. Cultural knowledge pertaining to the application of medicinal plants in the treatment of parasitic infection represents a vital role in the discovery of safe and natural chemotherapeutic agents against toxoplasmosis [9].…”

Section: Introductionmentioning

confidence: 99%