The challenge of Chagas' disease chemotherapy: An update of drugs assayed against Trypanosoma cruzi

Castro, Solange L. de

doi:10.1016/0001-706x(93)90021-3

Cited by 130 publications

(97 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 Both drugs have limitations: efficacy is restricted to the acute phase of the disease, there are serious toxic side effects, patients require long courses of treatment, and there is marked variation in the drug sensitivity of parasite populations. 2 Many different classes of drugs have been studied in the search for alternative therapies, 3 and much current interest has focused upon the potential of sterol biosynthesis inhibitors, for example, antifungal azoles. [4][5][6] The polyene antibiotic amphotericin B has previously been shown to have activity in vitro against amastigotes, trypomastigotes, and epimastigotes of T. cruzi, 3 as well as against trypomastigotes at 4ЊC in studies to find new drugs to prevent transmission of Chagas disease by blood transfusion.…”

mentioning

confidence: 99%

“…2 Many different classes of drugs have been studied in the search for alternative therapies, 3 and much current interest has focused upon the potential of sterol biosynthesis inhibitors, for example, antifungal azoles. [4][5][6] The polyene antibiotic amphotericin B has previously been shown to have activity in vitro against amastigotes, trypomastigotes, and epimastigotes of T. cruzi, 3 as well as against trypomastigotes at 4ЊC in studies to find new drugs to prevent transmission of Chagas disease by blood transfusion. 7,8 Amphotericin B also exhibited activity against T. cruzi in infected mice, 9 although this was not confirmed in another study.…”

mentioning

confidence: 99%

“…10 However, there have been limited clinical studies on the therapeutic efficacy of amphotericin B in Chagas disease. 3 Amphotericin B exerts its selective activity against fungi as well as protozoa Leishmania and T. cruzi through a higher affinity for ergosterol and ergosterol-like sterols, the predominant membrane sterol in these eukaryotic microorganisms, than for cholesterol, the predominant sterol in mammalian cells. [11][12][13] The use of amphotericin B has been limited by its high toxicity.…”

mentioning

confidence: 99%

See 2 more Smart Citations

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

Yardley¹,

Croft²

1999

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. The activities of four amphotericin B formulations, Fungizone , AmBisome , Amphocil , and Abelcet , were compared in vitro and in vivo against Trypanosoma cruzi infections. In vitro, Fungizone and Amphocil were highly active against T. cruzi Y strain amastigotes in macrophages with 50% effective dose (ED 50 ) values of 0.027-0.028 g/ml, which were 7-fold and 42-fold more active than AmBisome and Abelcet, respectively. In vitro activities of all formulations against T. cruzi amastigotes in Vero cells were similar, with ED 50 values in the range of 2.0-4.2 g/ml. Acute infections of the T. cruzi Y strain in BALB/c mice were suppressed in all animals by a single 25 mg/kg dose of the liposomal formulation AmBisome. At the same dose, the two other lipid formulations, Amphocil and Abelcet, increased the survival rate but did not suppress infection in all animals.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

Yardley¹,

Croft²

1999

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…The only trypanocidal substance currently used to prevent the infection by this route is gentian violet, but its use is limited due to undesirable effects on the patients (Dias, 1993). The treatment of Chagas' disease is still a challenge, since the only current available drug (benznidazole) has strong side effects (de Castro, 1993). Thus, the search for more efficient and less toxic drugs is needed to control this disease.…”

Section: Introductionmentioning

confidence: 99%

Trypanocidal activity of flavonoids and limonoids isolated from Myrsinaceae and Meliaceae active plant extracts

Leite¹,

Neto²,

Ambrozin³

et al. 2010

Rev. bras. farmacogn.

View full text Add to dashboard Cite

RESUMO: "Atividade tripanocida de flavonoides e limonoides isolados de extratos ativos de plantas de Myrsinaceae e Meliaceae". A atividade de extratos brutos de três espécies de Rapanea (Myrsinaceae) e de Cipadessa fruticosa (Meliaceae) foi avaliada in vitro contra formas tripomastigotas de Trypanosoma cruzi. Foram obtidos 33 extratos de diferentes órgãos das espécies estudadas, sendo que onze deles apresentaram atividades significantes (% de lise > 50) nos ensaios realizados. O fracionamento de um extrato ativo dos galhos de R. lancifolia (99,5%) resultou no isolamento de dois flavonoides (quercetina e taxifolina), que apresentaram baixa atividade tripanocida. De um extrato ativo dos frutos de C. fruticosa (97,7%) foram isolados os limonoides mexicanolídeos cipadesina, mexicanolídeo, febrifugina e cipadesina A, que foram moderadamente ativos sobre T. cruzi. Além disso, outros dois flavonoides (flavona e 7-metoxiflavona), previamente ensaiados contra T. cruzi, foram isolados do extrato hexânico dos galhos de C. fruticosa (100%). Os resultados obtidos aqui sugerem que as plantas avaliadas podem constituir fontes de novas substâncias ativas sobre o T. cruzi.Unitermos: Myrsinaceae, Meliaceae, atividade tripanocida, flavonoides, limonoides. ABSTRACT:The activity of crude extracts of three Rapanea species (Myrsinaceae) and Cipadessa fruticosa (Meliaceae) was evaluated in vitro against the trypomastigote forms of Trypanosoma cruzi. Thirty-three extracts from different organs of these species were assayed and eleven of them showed significant activity (lysis % >50). The fractionation of an active extract from branches of R. lancifolia (99.5%) led to the isolation of two flavonoids: quercetin and taxifolin, which have weak trypanocidal activity. Additionally, one active extract from fruits of C. fruticosa (97.7%) afforded mexicanolide limonoids: cipadesin, mexicanolide, febrifugin and cipadesin A, that were slightly active on T. cruzi. Moreover, other two flavonoids (flavone and 7-methoxyflavone), previously assayed against T. cruzi, were isolated from the hexane extract from branches of C. fruticosa (100%). The results presented here suggest that the plants evaluated could be a source of new active compounds against T. cruzi.

show abstract

“…Although there are several drugs on trial for the chemotherapy of human leishmaniasis many are new formulations of old drugs. There are few drugs of promise for either HAT or Chagas disease and the situation is precarious (De Castro 1993, Wang 1995.…”

mentioning

confidence: 99%

Pharmacological Approaches to Antitrypanosomal Chemotherapy

Croft

1999

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

The challenge of Chagas' disease chemotherapy: An update of drugs assayed against Trypanosoma cruzi

Cited by 130 publications

References 69 publications

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

Trypanocidal activity of flavonoids and limonoids isolated from Myrsinaceae and Meliaceae active plant extracts

Pharmacological Approaches to Antitrypanosomal Chemotherapy

Contact Info

Product

Resources

About