The sterols of Trypanosoma cruzi and Crithidia fasciculata

Korn, Edward D.; Brand, Theodor von; Tobie, Eleanor Johnson

doi:10.1016/0010-406x(69)92137-9

Cited by 63 publications

(27 citation statements)

References 12 publications

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“…In agreement with this hypothesis it has been shown that ∆ 24 (25) sterol methyl transferase inhibitors have a potent antiproliferative effect on Crithidia fasciculata in vitro [42] and on T. cruzi in vitro and in vivo [43].…”

Section: Possible Approaches To the Chemotherapy Of Chagas' Diseasesupporting

confidence: 64%

“…Although several hypotheses on the mode of action have been proposed for both the imidazole and triazole antifungal agents, all of them interfere with sterol biosynthesis and belong with some other nitrogen heterocycle-containing antifungals to the class of ergosterol biosynthesis inhibitors [24]. Since T. cruzi contains ergosterol [25,26], it was not unexpected that, when two of these inhibitors, miconazole and econazole, were initially tested against this parasite, they showed a potent growth inhibitory action parallel to a decrease in its 5,7-diene sterol content [27]. Later studies showed that ketoconazole, and other potent antimycotic azoles were also active in protecting mice against lethal infections with T. cruzi [28,29], in inhibiting…”

Section: Sterol Metabolismmentioning

confidence: 99%

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Recent Developments in the Chemotherapy of Chagas Disease

Docampo¹

2001

CPD

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Chagas disease remains an important health problem in the Americas. Advances are being made in parts of South America in blocking transmission from insect vectors or blood transfusion, but more effective chemotherapy is needed for the millions who are already infected. This is especially important since recent results have indicated that treatment is beneficial for the elimination of the chronic course of the disease. The rational development of new drugs depends on the identification of differences between human metabolism and that of the causative parasite, Trypanosoma cruzi. Recent developments in the study of the basic biochemistry of the parasite have allowed the identification of novel targets for chemotherapy, such as sterol metabolism, protein prenylation, proteases, and phospholipid metabolism, and these are the subject of this review.

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Section: Possible Approaches To the Chemotherapy Of Chagas' Diseasesupporting

confidence: 64%

Section: Sterol Metabolismmentioning

confidence: 99%

Recent Developments in the Chemotherapy of Chagas Disease

Docampo¹

2001

CPD

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“…Recent studies by Korn, von Brand & Tobie (1969) have shown that Trypanosoma cruzi and Crithidia fasiculata, when grown on serum or defined media, are capable of producing several different sterols with the 5,7-diene structure in addition to ergosterol, which was expected. These findings in closely related organisms suggest that the 5,7-diene in Leishmania donovani may not be ergosterol but a mixture of several related sterols.…”

Section: Discussionmentioning

confidence: 78%

Occurrence of a 5,7-Diene Sterol in Leishmania donovani

Kuwahara

Pinto

Kazan

1971

Journal of General Microbiology

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Ergosterol, a 5,7-diene sterol, has been isolated from a number of the Trypanosomidae. It is the major sterol in Crithidia fasiculuta (Kusel & Weber, 1965) Williamson & Ginger, 1965) and concluded that cholesterol is the major sterol in the organism. However, Ghosh (1963) working with membranes from L. donovani, found a sterol which was 'fastreacting' with the Lieberman-Buchard reagent indicating the presence of a A' or As structure (Cook & Rattray, 1958), but did not obtain an ultraviolet spectrum showing the presence of a 5,7-diene and concluded that 5,7-dienes and cholesterol were absent.Our studies on the lipids of Leishmania donovani have produced results contrary to those reported by Williamson (1963) and we have obtained an ultraviolet spectrum confirming the presence of 5,7-dienes in the sterol fraction from L. donovani. METHODSLeishmania donovani (National Institutes of Health, U.S.A., strain, obtained from Dr E. J. Tobie) was cultured in a diphasic medium consisting of an agar supplemented brain-heart infusion agar (Difco) containing 2 % (w/v) glucose and 10 % (v/v) defibrinated rabbit blood as the solid base. Locke's solution was used as an overlay. The cultures were grown at room temperature for 8 to 10 days before harvesting by centrifugation at 3500 g for 10 min. at room temperature.The harvested organisms were suspended in 0-1 culture volumes of IOO mM-KCl at 5" and recentrifuged.The washed organisms were resuspended in 0-01 culture volurneof cold IOO mM KCL and extracted by the method of Bligh & Dyer (1959).The dry, total lipid extract from I O~O organisms was added to a 15 g. column of silicic acid (CC-4; Mallinkrodt Chemical) and the neutral lipids were eluted with chloroform. Chloroform was removed with a rotary evaporator and the neutral lipids were dissolved in hexane. The sample was then chromatographed on a 10 g. column of Florisil (Floridin Co., Tallahassee, Florida) using the elution scheme given by Carroll (1961). The sterols were eluted with 15 % (v/v) diethyl ether in hexane.Thin-layer chromatography was performed on silica gel G (Merck, Darmstat, Germany).

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“…They function as inhibitors of key pathways in the synthesis of lipids and steroids, respectively , Roberts et al 2003. The lipid metabolism of trypanosomatids has been studied since the 60s (Korn & Greenblatt 1963, Korn et al 1969, Dixon et al 1971, 1972 but the identification of key differences between the host and the parasite, as well as the study of the enzymes themselves, has not been fully achieved. The sterol biosynthesis pathway has been better characterised, especially because of its similarity with the corresponding pathways in fungi and yeasts where the main sterol is ergosterol (Roberts et al 2003).…”

Section: Lipid Metabolismmentioning

confidence: 99%