In vitro effects of suramin on Trypanosoma cruzi

Bisaggio, Danielle F. R.; Adade, Camila M.; Souto-Padrón, Thaïs

doi:10.1016/j.ijantimicag.2007.11.001

Cited by 19 publications

(18 citation statements)

References 13 publications

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“…After 96 h this compound considerably reduced the number of parasites, by causing progressive injury compared with untreated cells. A dose-dependent effect was observed, and at this time the IC 50 value was 59 µmol L -1 (Figure 1), whereas the standard drug benznidazole showed an IC 50 of 7 µmol L -1 . 47 Other terpene derivatives showed some trypanocidal activity, such as dehydrozaluzanin C isolated from Munnozia maronii (Asteraceae), that showed IC 90 between 10-205 µmol L -1 against different strains of T. cruzi.…”

Section: Biological Studiesmentioning

confidence: 90%

“…After 96 h of treatment, the 50% cytotoxic concentration was 347 µmol L -1 ( Figure 2). Therefore, by the selectivity index (SI) ratio (CC 50 for LLCMK 2 /IC 50 for parasite), acanthoic acid (1) was more selective against the parasite than against mammal cells, with a SI of 5.9.…”

Section: Biological Studiesmentioning

confidence: 99%

“…16,[48][49] Several synthetic compounds have also shown trypanocidal activity. 50,51 Acanthoic acid (1) at 3 µmol L -1 (the lowest concentration tested) displayed a growth inhibition of parasites of 13.6%, while at the highest concentration (331 µmol L -1 ), over 90% of the cells were affected. Therefore, the 50% inhibition concentration was determined at 59 µmol L -1 .…”

Section: Biological Studiesmentioning

confidence: 99%

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Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

Pinheiro

Xavier

Souza

et al. 2009

J. Braz. Chem. Soc.

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O presente trabalho descreve o isolamento, a partir do caule de Annona amazonica, do ácido acantóico, um diterpeno do tipo pimaradieno que possui várias e importantes atividades biológicas descritas na literatura. Neste estudo foi verificado que este composto apresenta significante atividade tripanocida contra as formas epimastigotas de Trypanosoma cruzi. Também foi constatado que este diterpeno é o constituinte majoritário da planta, encontrado em cerca de 65% do extrato hexânico, demonstrando que A. amazonica é uma nova fonte natural renovável desta substância. Além do ácido acantóico, a investigação química resultou no isolamento dos alcalóides liriodenina e cassiticina, entre outros compostos, tais como terpenos, esteróides e ácidos graxos. Adicionalmente, é descrita a completa e inequívoca atribuição dos deslocamentos químicos de RMN de 1 H e 13 C da cassiticina.The present work reports the isolation of acanthoic acid, a promising pimaradiene-type diterpene with several important biological activities described in the literature, from the stems of Annona amazonica. We found that acanthoic acid has significant trypanocidal activity against the epimastigote forms of Trypanosoma cruzi. This diterpene is the major constituent of the plant, comprising at least 65% of the hexane extract, demonstrating that A. amazonica is a new renewable natural source for this compound. The chemical investigation also resulted in the isolation of the alkaloids liriodenine and cassythicine, and other compounds including terpenes, sterols, and fatty acids. Additionally, the complete and unequivocal 1 H and 13 C NMR chemical shift assignments for cassythicine are provided. Keywords: Annona amazonica, Annonaceae, acanthoic acid, cassythicine, trypanocidal activity IntroductionThe family Annonaceae, comprised of tropical and subtropical species with about 135 genera and more than 2500 species and widely distributed in South and Central America, Africa, Asia, and Australia, 1 is known for its edible fruits and the medicinal properties of several species. 2 In Brazil, there are 26 genera with about 260 species, including the genus Annona, which contains approximately 120 species. 3 Chemical investigations of species of Annonaceae have revealed their high chemical diversity in terms of secondary metabolites, such as alkaloids, acetogenins, terpenoids and lactones. These compounds have shown important biological activities, including antiparasitic, in particular against Leishmania sp., Plasmodium falciparum, and Trypanosoma cruzi. [4][5][6][7][8][9][10][11][12] Annona amazonica R.E. Fries is a tropical tree that grows up to 20-25 m tall and 35-60 cm in diameter, and is found from Panama to South America. In Brazil this species commonly occurs in the Amazon, mainly in the states of Amazonas and Pará. 13 To the best of our knowledge, only one previous phytochemical study has described the isolation and identification of cyanogenic constituents from this species. 14 Here we describe the isolation and structural identification of the chemica...

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Section: Biological Studiesmentioning

confidence: 90%

Section: Biological Studiesmentioning

confidence: 99%

Section: Biological Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

Pinheiro

Xavier

Souza

et al. 2009

J. Braz. Chem. Soc.

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“…Treatment of T. cruzi with suramin, a symmetrical polysulfonated derivative of urea used in the prophylactic treatment of human trypanosomiasis in Africa, caused increased activity of a Mg 2+ ecto-ATPase and the FRA antigen and redistribution of negative surface charges. Alterations in extracellular components in the region of adhesion between the cell body and the flagellum and an increase in the adhesion of epimastigotes to resident macrophages were also observed [92,98,99] (Fig. 2L). …”

Section: The Cell Surfacementioning

confidence: 77%

“…cruzi trypomastigotes treated with suramin exhibited an altered nuclear division pattern and frequently presented irregular or multiple nuclei [92]. Vinblastin-resistant L. amazonensis also presented dysfunctional cytokinesis, in which the resistant promastigotes showed multiple nuclei [93].…”

Section: Nucleusmentioning

confidence: 99%

Contributions of Ultrastructural Studies to the Cell Biology of Trypanosmatids: Targets for Anti-Parasitic Drugs

Almeida¹,

Souto-Padrón

2010

TOPARAJ

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Protozoan parasites cause disease in humans worldwide, and many fall into the genera Trypanosoma and Leishmania; these parasites are responsible for African trypanosomiasis, Chagas disease and the different forms of Leishmaniasis. Strategies for the development of new drugs against these protozoans have been based on their cell biology and biochemistry complemented by the use of electron microscopy. Trypanosoma and Leishmania have special organelles that are involved in metabolic pathways, which are very distinct from those in mammalian cells; these organelles are potential drug targets. Scanning and transmission electron microscopy can identify not only the target organelles but also alterations to the cell surface and ultrastructural changes that characterize distinct forms of programmed cell death.

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Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

et al. 2011

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Herein, we have aimed to explore the effects of pepstatin A, a powerful aspartic protease inhibitor, on Trypanosoma cruzi, the etiologic agent of Chagas' disease. Pepstatin A arrested the proliferation of epimastigotes of T. cruzi (clone Dm28c, TcI lineage), in both dose- and time-dependent manner. The IC(50) value was calculated to be 36.2 μM after 96 h of parasite-drug contact. The parasite treatment with pepstatin A resulted in significant morphological alterations, including parasites becoming round in shape, reduction (≈25%) of the parasite size, and parasites presenting parts or the whole flagellum detached from the cell body. Cell lysis was not observed, resulting in a trypanostatic effect. The treatment of different T. cruzi strains, belonging to distinct phylogenetic lineages, with pepstatin A at 36.2 μM resulted in growth inhibition as follows: 28% to Y (TcII), 45% to CL Brener (TcII), 45.4% to 4167 (Z3), and 26.4% to 3663 (Z3) strains. The hydrolysis of a cathepsin D fluorogenic substrate (7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D: -Arg-amide) by T. cruzi epimastigote extract was inhibited (≈65%) by pepstatin A at 10 μM, suggesting that an aspartic protease may be the intracellular target of this inhibitor. Curiously, pepstatin A induced an increase of 54% and 98%, respectively, in the surface expression of gp63- and calpain-related molecules in epimastigotes, but not in the cruzipain level, as well as stimulated the epimastigote-to-trypomastigote differentiation in a dose-dependent manner. However, approximately 45% of the trypomastigotes had their flagellum detached from the cell body. These results contribute to understand the possible role of aspartic proteases in the physiology of T. cruzi cells, adding new in vitro insights into the possibility of exploiting aspartic protease as promising targets to treat Chagas' disease.

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In vitro effects of suramin on Trypanosoma cruzi

Cited by 19 publications

References 13 publications

Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

Contributions of Ultrastructural Studies to the Cell Biology of Trypanosmatids: Targets for Anti-Parasitic Drugs

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

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