Indole Alkaloids from Aspidosperma rigidum and A. schultesii and their Antiparasitic Effects

2011 ◽  
Vol 66 (5-6) ◽  
pp. 225-234 ◽  
Author(s):  
Matías Reina ◽  
Wilfredo Ruiz-Mesia ◽  
Lastenia Ruiz-Mesia ◽  
Rafael Martínez-Díaz ◽  
Azucena González-Coloma
Keyword(s):  
Medicinal Plants ◽  
Trypanosoma Cruzi ◽  
Leishmania Infantum ◽  
Mammalian Cells ◽  
Indole Alkaloids ◽  
Antiparasitic Activity ◽  
Specific Cytotoxicity ◽  
Oxindole Alkaloids

Five oxindole alkaloids, three plumerane-type alkaloids, subtype haplophitine, and one aspidospermatane-type alkaloid, subtype tubotaiwine, were isolated from the medicinal plants Aspidosperma rigidum and A. schultesii. One compound was identified as the transoid conformer of 18-oxo-O-methylaspidoalbine which was not previously described. The antiparasitic activity of all compounds against Trypanosoma cruzi and Leishmania infantum and their non-specific cytotoxicity against mammalian cells were also determined.

scholarly journals Antiparasitic Indole Alkaloids from Aspidosperma desmanthum and A. spruceanum from the Peruvian Amazonia

2014 ◽  
Vol 9 (8) ◽  
pp. 1934578X1400900
Author(s):  
Matías Reina ◽  
Lastenia Ruiz-Mesia ◽  
Wilfredo Ruiz-Mesia ◽  
Frida Enriqueta Sosa-Amay ◽  
Leonor Arevalo-Encinas ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Indole Alkaloids ◽  
2D Nmr ◽  
Stem Bark ◽  
Spectroscopic Techniques ◽  
Root Bark ◽  
Antiparasitic Activity ◽  
Specific Cytotoxicity ◽  
First Time ◽  
Selective Activity

Twenty-three indole alkaloids were isolated from Aspidosperma desmanthum and A. spruceanum. Alkaloids 1-4 were isolated from the leaves, 5-8 from the stem bark and 9-15 from the root bark of A. desmanthum. Alkaloids 5, 11, 16, 17 and 19 were isolated from the stem bark, 18 and 20-22 from the root bark and 23 from the flowers of A. spruceanum. Compounds 4, 14, and 15 have not been previously reported as natural products while 16 and 20 have been isolated for the first time from the genus Aspidosperma. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). The antiparasitic activity of these compounds was tested against Trypanosoma cruzi and Leishmania infantum and their non-specific cytotoxicity on mammalian cells. The most active compounds were 10, 12, 13, and 14 from A. desmanthum, and 19, 21 and 22 from A. spruceanum. Aspidolimine (10) aspidocarpine (12) and tubotaiwine (21) showed selective activity against L. infantum.

New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum

2017 ◽  
Vol 90 (5) ◽  
pp. 1007-1011 ◽  
Author(s):  
Marina T. Varela ◽  
Marta L. Lima ◽  
Mariana K. Galuppo ◽  
Andre G. Tempone ◽  
Alberto de Oliveira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Leishmania Infantum ◽  
Antiparasitic Activity

Discovery of 2-aminopyridine Derivatives with Antichagasic and Antileishmanial Activity Using Phenotypic Assays

2020 ◽  
Vol 17 (7) ◽  
pp. 867-872
Author(s):  
Daiane Yukie Tezuka ◽  
Sergio de Albuquerque ◽  
Carlos Alberto Montanari ◽  
Andrei Leitão
Keyword(s):  
Flow Cytometry ◽  
Trypanosoma Cruzi ◽  
Cancer Cells ◽  
Cell Line ◽  
Leishmania Infantum ◽  
Fibroblast Cell ◽  
Leishmania Amazonensis ◽  
Fibroblast Cell Line ◽  
Antiparasitic Activity ◽  
Promastigote Form

Background: Compounds previously studied as anticancer were screened against trypomastigotes to access the bioactivity. The epimastigote form of Trypanosoma cruzi Y strain and the promastigote form of Leishmania amazonensis and Leishmania infantum were used in this work. Methods: Cell-based assays were performed to access the bioactivity of the compounds using MTT and the flow cytometry methods. Results: Neq0438, Neq0474 and Neq0440 had the highest potency, with EC50 of 39 μM (L. amazonensis), 52 μM (T. cruzi) and 81 μM (T. cruzi), respectively. These molecules were inactive for Balb/C fibroblast cell line at concentrations above 250 μM, showing selectivity for the parasites. Conclusion: This is the first report that demonstrates antiparasitic activity for the 2-aminopyridine scaffold, with cross-activity against cancer cells.

Activity of β-Caryophyllene Oxide Derivatives Against Trypanosoma cruzi, Mammalian Cells, and Horseradish Peroxidase

2021 ◽  
Author(s):  
Gisele Bulhões Portapilla ◽  
Luiz Miguel Pereira ◽  
Rafael Augusto Soldi ◽  
Péricles Gama Abreu Filho ◽  
Inara Fernanda Lage Gallo ◽  
...  
Keyword(s):  
Horseradish Peroxidase ◽  
Trypanosoma Cruzi ◽  
Mammalian Cells ◽  
Caryophyllene Oxide

scholarly journals Neurotrophin Receptor TrkC Is an Entry Receptor for Trypanosoma cruzi in Neural, Glial, and Epithelial Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 4081-4087 ◽  
Author(s):  
Craig Weinkauf ◽  
Ryan Salvador ◽  
Mercio PereiraPerrin
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Mammalian Cells ◽  
Chinese Hamster ◽  
Neuronal Cell ◽  
Host Cells ◽  
Neurotrophin Receptor ◽  
Content Type

ABSTRACTTrypanosoma cruzi, the agent of Chagas' disease, infects a variety of mammalian cells in a process that includes multiple cycles of intracellular division and differentiation starting with host receptor recognition by a parasite ligand(s). Earlier work in our laboratory showed that the neurotrophin-3 (NT-3) receptor TrkC is activated byT. cruzisurfacetrans-sialidase, also known as parasite-derived neurotrophic factor (PDNF). However, it has remained unclear whether TrkC is used byT. cruzito enter host cells. Here, we show that a neuronal cell line (PC12-NNR5) relatively resistant toT. cruzibecame highly susceptible to infection when overexpressing human TrkC but not human TrkB. Furthermore,trkCtransfection conferred an ∼3.0-fold intracellular growth advantage. Sialylation-deficient Chinese hamster ovarian (CHO) epithelial cell lines Lec1 and Lec2 also became much more permissive toT. cruziafter transfection with thetrkCgene. Additionally, NT-3 specifically blockedT. cruziinfection of the TrkC-NNR5 transfectants and of naturally permissive TrkC-bearing Schwann cells and astrocytes, as did recombinant PDNF. Two specific inhibitors of Trk autophosphorylation (K252a and AG879) and inhibitors of Trk-induced MAPK/Erk (U0126) and Akt kinase (LY294002) signaling, but not an inhibitor of insulin-like growth factor 1 receptor, abrogated TrkC-mediated cell invasion. Antibody to TrkC blockedT. cruziinfection of the TrkC-NNR5 transfectants and of cells that naturally express TrkC. The TrkC antibody also significantly and specifically reduced cutaneous infection in a mouse model of acute Chagas' disease. TrkC is ubiquitously expressed in the peripheral and central nervous systems, and in nonneural cells infected byT. cruzi, including cardiac and gastrointestinal muscle cells. Thus, TrkC is implicated as a functional PDNF receptor in cell entry, independently of sialic acid recognition, mediating broadT. cruziinfection bothin vitroandin vivo.

scholarly journals Mammalian cell invasion and intracellular trafficking by Trypanosoma cruzi infective forms

2005 ◽  
Vol 77 (1) ◽  
pp. 77-94 ◽  
Author(s):  
Renato A. Mortara ◽  
Walter K. Andreoli ◽  
Noemi N. Taniwaki ◽  
Adriana B. Fernandes ◽  
Claudio V. da Silva ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Mammalian Cells ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
Mammalian Host ◽  
Target Cells ◽  
Sylvatic Cycle ◽  
Final Destination ◽  
Different Strains

Trypanosoma cruzi, the etiological agent of Chagas’ disease, occurs as different strains or isolates that may be grouped in two major phylogenetic lineages: T. cruzi I, associated with the sylvatic cycle and T. cruzi II, linked to the human disease. In the mammalian host the parasite has to invade cells and many studies implicated the flagellated trypomastigotes in this process. Several parasite surface components and some of host cell receptors with which they interact have been identified. Our work focused on how amastigotes, usually found growing in the cytoplasm, can invade mammalian cells with infectivities comparable to that of trypomastigotes. We found differences in cellular responses induced by amastigotes and trypomastigotes regarding cytoskeletal components and actin-rich projections. Extracellularly generated amastigotes of T. cruzi I strains may display greater infectivity than metacyclic trypomastigotes towards cultured cell lines as well as target cells that have modified expression of different classes of cellular components. Cultured host cells harboring the bacterium Coxiella burnetii allowed us to gain new insights into the trafficking properties of the different infective forms of T. cruzi, disclosing unexpected requirements for the parasite to transit between the parasitophorous vacuole to its final destination in the host cell cytoplasm.

scholarly journals Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents Against Trypanosoma cruzi

2021 ◽  
Author(s):  
Jean A. Bernatchez ◽  
Yun-Seo Kil ◽  
Elany Barbosa da Silva ◽  
Diane Thomas ◽  
Laura-Isobel McCall ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasitic Infection ◽  
Antiparasitic Activity ◽  
Gastrointestinal Pathology ◽  
Phenotypic Screen ◽  
Benthic Environment ◽  
Intracellular Amastigote ◽  
Kinetoplastid Parasite

Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid parasite Trypanosoma cruzi, have yet to be developed. Benznidazole and nifurtimox, which are currently the only available drugs against T. cruzi, are associated with severe adverse effects and questionable efficacy in the late stage of the disease. Natural products have proven to be a rich source of new chemotypes for other infectious agents. We utilized a microscopy-based high-throughput phenotypic screen to identify inhibitors of T. cruzi from a library of natural product samples obtained from fungi procured through a Citizen Science Soil Collection Program (https://whatsinyourbackyard.org/), and the Great Lakes (USA) benthic environment. We identified five leucinostatins (A, B, F, NPDG C and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi. Leucinostatin B also showed in vivo efficacy in a mouse model of Chagas disease. Given prior reports that leucinostatins A and B have antiparasitic activity against the related kinetoplastid T. brucei, our findings suggest a potential cross-trypanocidal compound class and provide a platform for further chemical derivatization of a potent chemical scaffold against T. cruzi.

scholarly journals Antiparasitic Metabolites from Hyptis brevipes, a Tacana Medicinal Plant

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400 ◽  
Author(s):  
Ivan Limachi ◽  
Claudia Condo ◽  
Camila Palma ◽  
Nelida Nina ◽  
Efrain Salamanca ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Nmr Spectroscopy ◽  
Medicinal Plants ◽  
Medicinal Plant ◽  
Trypanosoma Cruzi ◽  
Hela Cells ◽  
Giardia Lamblia ◽  
Structure Elucidation ◽  
Intestinal Parasites ◽  
Active Constituents

A bioassay screening against protozoa parasites of several Tacana medicinal plants gave Hyptis brevipes (Id'ene eidhue), traditionally used as decoction for intestinal parasites, as the most active extract. In this work we did a bioguided isolation of active constituents found in leaves. Structure elucidation was carried out by NMR spectroscopy and MS spectrometry analyses. Active constituents showed differentiated activity towards Giardia lamblia, Trypanosoma cruzi, several Leishmania strains, Plasmodium falciparum and cytotoxicity against HeLa cells. Brevipolide H (1) was the less cytotoxic and best antiparasitic, while the catechol derivative (2) the most active and cytotoxic.

scholarly journals Inhibition of Trypanosoma cruzi growth in mammalian cells by purine and pyrimidine analogs.

1996 ◽  
Vol 40 (11) ◽  
pp. 2455-2458 ◽  
Author(s):  
J Nakajima-Shimada ◽  
Y Hirota ◽  
T Aoki
Keyword(s):  
Trypanosoma Cruzi ◽  
Growth Inhibition ◽  
Host Cell ◽  
Culture System ◽  
Mammalian Cells ◽  
Screening Method ◽  
Host Cells ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Pyrimidine Analogs

Trypanosoma cruzi, the causative agent of Chagas' disease, exhibits two different developmental stages in mammals, the amastigote, an intracellular form that proliferates in the cytoplasm of host cells, and the trypomastigote, an extracellular form that circulates in the bloodstream. We have already established an in vitro culture system using mammalian host cells (HeLa) infected with T. cruzi in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of anti-T. cruzi agents that would ideally prove to be effective against trypanosomes with no toxicity to the host cell. Of the purine analogs tested, allopurinol markedly inhibited the growth of amastigotes in a dose-dependent manner, with no lethal effect on trypomastigotes. 3'-Deoxyinosine and 3'-deoxyadenosine also suppressed T. cruzi growth inside the host cell, with the concentrations causing 50% growth inhibition being 10 and 5 microM, respectively, in contrast to a concentration causing 50% growth inhibition of 3 microM for allopurinol. Among the pyrimidine analogs examined, 3'-azido-3'-deoxythymidine (zidovudine) significantly reduced the growth of the parasite at concentrations as low as 1 microM. The anti-human immunodeficiency virus agents 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine caused a decrease in amastigote growth, while 2',3'-dideoxycytidine and 2',3'-dideoxyuridine had no inhibitory effect. When Swiss 3T3 fibroblasts were used as host cells, allopurinol, 3'-deoxyinosine, 3'-deoxyadenosine, and 3'-azid-3'-deoxythymidine also markedly inhibited T. cruzi proliferation. These results indicate that our culture system is useful as a primary screening method for candidate compounds against T. cruzi on the basis of two criteria, namely, intracellular replication by the parasite and host-cell infection rate.

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