Trypanosoma cruzi: Antiproliferative effect of indole phytoalexins on intracellular amastigotes in vitro

Mezencev, Roman; Galizzi, Melina; Kutschy, Peter; Docampo, Roberto

doi:10.1016/j.exppara.2009.01.013

Cited by 44 publications

(30 citation statements)

References 36 publications

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“…The statistical significance between IC 50 values was determined with a paired 2-tailed t-test ( p < 0.05), as reported previously (Mezencev et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Martı́nez

Nogueda

Martínez‐Hernández

et al. 2013

Vector-Borne and Zoonotic Diseases

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Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and it affects as many as 10 million people in North and South America, where it represents a major public health problem. T. cruzi is a parasite with high genetic diversity, and it has been grouped into 6 discrete typing units (DTUs), designated as T. cruzi I (TcI) to T. cruzi VI (TcVI). Mexican isolates from humans and from vector insects have been primarily found to be TcI, and these isolates are likely to be the strains that cause the clinical manifestations observed in Mexico. However, genetic characterization and drug susceptibility assays are limited in Mexican TcI strains. In this work, 24 Mexican T. cruzi strains, obtained primarily from humans, were studied with 7 locus microsatellites and mini-exon gene by PCR. Also, drug susceptibility was evaluated by growth and mobility assays. All of the human strains belonged to TcI, and they could be further grouped through microsatellite analysis into 2 subgroups (microsatellite genotypes 1 and 2), which were not related to the host clinical status or biological origin of the strain. Two strains, both from wild mammals, belonged to the TcII-TcVI groups; these strains and the CL Brener strain constituted microsatellite genotype 3. The number of alleles in each locus was lower than reported for South American strains, and a departure from the Hardy-Weinberg equilibrium was observed. The susceptibility of these strains to nifurtimox and benznidazole was heterogeneous. T. cruzi strains characterized as microsatellite genotypes 2 and 3 were significantly more susceptible to benznidazole than strains of microsatellite genotype 1. Only 1 Mexican strain resistant to both drugs was found in this study.

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“…The statistical significance between IC 50 values was determined with a paired 2-tailed t-test ( p < 0.05), as reported previously (Mezencev et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Martı́nez

Nogueda

Martínez‐Hernández

et al. 2013

Vector-Borne and Zoonotic Diseases

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“…The higher shielding of H-2 in the cis-diastereoisomers is probably caused by anisotropic shielding by the C=N double bond of the thiazoline ring. This correlation is valid for trans-and cis-diastereoisomers of 1-methoxyspirobrassinol (3), 7 1-methoxyspirobrassinol methyl ether (4) 7,11 and 1-Bocspirobrassinol (29), 12 in which the diastereoisomeric structures were confirmed by NOE experiments. This consistent chemical shift difference was observed in CDCl3 or DMSO-d6.…”

Section: Methodsmentioning

confidence: 70%

“…27,28 1-Methoxybrassinin (5a) displayed significant antiproliferative effect on intramolecular amastigotes of Trypanosoma cruzi and demonstrated a higher potency than shown by the currently used antichagasic agents (nifurtimox, benznidazol). 29 Kristofikova et al documented the in vitro effect of anti-aggregation of spirobrassinin [(±)-1] in the cerebrospinal fluid of patients with multiple sclerosis. 30 In this paper we describe our investigations into the diastereoselectivity of spirocyclization of 1-methoxybrassinin (5a) in the presence of various alcohols as nucleophiles, in various solvents and at various temperatures.…”

Section: (±)-3a and Cis-(±)-3b With Cro3 12 Or A Mixture Of Diastereomentioning

confidence: 99%

Spirocyclization reactions and antiproliferative activity of indole phytoalexins 1-methoxybrassinin and its 1-substituted derivatives

Budovsk¹,

Piltov²,

Tischlerov³

et al. 2017

Arkivoc

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The effect of the reaction temperature and the solvent on the diastereoselectivity of the spirocyclization of 1-methoxybrassinin leading to 1-methoxyspirobrassinol methyl ether was studied. 1-Acyl derivatives of 1-methoxyspirobrassinol and 1-methoxyspirobrassinol methyl ether were prepared by the bromine-mediated spirocyclization reactions of derivatives of brassinin bearing an acyl group on the indole nitrogen with water or methanol as nucleophilic agents. The cyclization of 1-acyl derivatives of brassinin afforded the trans-diastereoisomer as the major product, whereas using 1-methoxybrassinin afforded the cis-and trans-isomers in a ratio near to 1:1. Bromospirocyclization of brassinin and 1-methylbrassinin in the presence of methanol resulted in the formation of spirobrassinin and 1-methylspirobrassinin. The newly synthesized analogues of indole phytoalexins exhibited more significant antiproliferative activity against human leukemia cell lines than the natural phytoalexins.

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“…The current chemotherapy for Chagas disease is still based on benznidazole (BNZ) (N-benzyl-2-nitroimidazole-1-yl acetamide) [4] ( Fig. 1a), which is very toxic and has low solubility [5,6], but complexation with cyclodextrins provides a way of increasing the solubility of drugs [7].…”

Section: Introductionmentioning

confidence: 99%

Study of benznidazole–cyclodextrin inclusion complexes, cytotoxicity and trypanocidal activity

Lyra

Sobrinho

Figueiredo

et al. 2011

J Incl Phenom Macrocycl Chem

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The current chemotherapy for Chagas disease is still based on benznidazole, which has low solubility, but complexation with cyclodextrins provides a way of increasing the solubility. The objective of this work was to characterize the inclusion complexes formed between benznidazole (BNZ) and randomly 2-methyled-b-cyclodextrin (RM-b-CD) in aqueous solution and study cytotoxicity and trypanocidal. BNZ:RM-b-CD solution complex systems were prepared and characterized using the phase solubility diagram, nuclear magnetic resonance and a photostability assays, also to investigate the in vitro trypanocidal activity with epimastigote forms of Trypanossoma cruzi and the study of cytotoxicity against mammal cells. The phase-solubility diagram displayed an A L -type feature, providing evidence of the formation of soluble inclusion complexes. The continuous variation method showed the existence of a complex with 1:1 stoichiometry. Toxicity assays demonstrated that inclusion complexes were able to reduce the toxic effects caused by benznidazole alone and that this did not interfere with the trypanocidal activity of the benznidazole. The use of inclusion complexes benznidazole:cyclodextrin is thus a promising alternative for the development of a safe and stable liquid formulation and a new option for the treatment of Chagas disease.

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Trypanosoma cruzi: Antiproliferative effect of indole phytoalexins on intracellular amastigotes in vitro

Cited by 44 publications

References 36 publications

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Microsatellite and Mini-Exon Analysis of Mexican Human DTU ITrypanosoma cruziStrains and Their Susceptibility to Nifurtimox and Benznidazole

Spirocyclization reactions and antiproliferative activity of indole phytoalexins 1-methoxybrassinin and its 1-substituted derivatives

Study of benznidazole–cyclodextrin inclusion complexes, cytotoxicity and trypanocidal activity

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