scholarly journals Naphthylisoquinoline alkaloids against malaria: evaluation of the curative potentials of dioncophylline C and dioncopeltine A against Plasmodium berghei in vivo.

1997 ◽  
Vol 41 (11) ◽  
pp. 2533-2539 ◽  
Author(s):  
G François ◽  
G Timperman ◽  
W Eling ◽  
L A Assi ◽  
J Holenz ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Oral Treatment ◽  
Toxic Effects ◽  
Effective Dosage ◽  
Radical Cure ◽  
Antiparasitic Activity ◽  
Antimalarial Agents ◽  
Naphthylisoquinoline Alkaloids ◽  
Relationship Of

Naphthylisoquinoline alkaloid-containing extracts from species of the families Dioncophyllaceae and Ancistrocladaceae and purified alkaloids derived therefrom were shown to exhibit antiparasitic activity in Plasmodium berghei-infected mice. Several extracts and alkaloids, especially dioncophylline C and dioncopeltine A, isolated from Triphyophyllum peltatum (Dioncophyllaceae), displayed high levels of activity. Dioncopeltine A was able to suppress parasitemia almost totally, while dioncophylline C cured infected mice completely after oral treatment with 50 mg kg of body weight(-1) day(-1) for 4 days without noticeable toxic effects. Analysis of the dose-response relationship of dioncophylline C revealed a 50% effective dosage (ED50) of 10.71 mg kg(-1) day(-1) under these conditions. Although four daily treatments with 50 mg kg(-1) day(-1) are needed to achieve radical cure, one oral dose is sufficient to kill 99.6% of the parasites. Intravenous application of dioncophylline C is even more effective, with an ED50 of 1.90 mg kg(-1) day(-1) and no noticeable toxic effects. The compound also suppressed more established P. berghei infections when orally applied at day 3 after infection. Both dioncopeltine A and dioncophylline C are active against the chloroquine-resistant P. berghei Anka CRS parasites. Sustained release of these compounds at 20 mg kg(-1) day(-1) by implanted miniosmotic pumps exhibited curative effects. The naphthylisoquinoline alkaloids are therefore promising new antimalarial agents.

scholarly journals Structure and Antiparasitic Activity Relationship of Alkylphosphocholine Analogues against Leishmania donovani

2020 ◽  
Vol 8 (8) ◽  
pp. 1117
Author(s):  
Humera Ahmed ◽  
Katharine C. Carter ◽  
Roderick A.M. Williams
Keyword(s):  
Chemical Structure ◽  
Leishmania Donovani ◽  
Oral Treatment ◽  
Parasite Load ◽  
Carbon Chain ◽  
Antiparasitic Activity ◽  
Relationship Of ◽  
Micromolar Range

Miltefosine (Milt) is the only oral treatment for visceral leishmaniasis (VL) but its use is associated with adverse effects, e.g., teratogenicity, vomiting, diarrhoea. Understanding how its chemical structure induces cytotoxicity, whilst not compromising its anti-parasitic efficacy, could identify more effective compounds. Therefore, we systemically modified the compound’s head, tail and linker tested the in vitro activity of three alkylphosphocholines (APC) series against Leishmania donovani strains with different sensitivities to antimony. The analogue, APC12, with an alkyl carbon chain of 12 atoms, was also tested for anti-leishmanial in vivo activity in a murine VL model. All APCs produced had anti-leishmanial activity in the micromolar range (IC50 and IC90, 0.46– > 82.21 µM and 4.14–739.89 µM; 0.01– > 8.02 µM and 0.09–72.18 µM, respectively, against promastigotes and intracellular amastigotes). The analogue, APC12 was the most active, was 4–10 fold more effective than the parent Milt molecule (APC16), irrespective of the strain’s sensitivity to antimony. Intravenous administration of 40 mg/kg APC12 to L. donovani infected BALB/c mice reduced liver and spleen parasite burdens by 60 ± 11% and 60 ± 19%, respectively, while oral administration reduced parasite load in the bone marrow by 54 ± 34%. These studies confirm that it is possible to alter the Milt structure and produce more active anti-leishmanial compounds.

scholarly journals Inhibition of In Vivo Growth of Plasmodium berghei by Launaea taraxacifolia and Amaranthus viridis in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Adewale Adetutu ◽  
Olubukola S. Olorunnisola ◽  
Abiodun O. Owoade ◽  
Peter Adegbola
Keyword(s):  
Survival Time ◽  
Plasmodium Berghei ◽  
Packed Cell Volume ◽  
Haematological Parameters ◽  
Antimalarial Agents ◽  
Western Africa ◽  
Methanolic Extracts ◽  
Crude Extracts ◽  
In Vivo Growth

Launaea taraxacifolia and Amaranthus viridis used by people of Western Africa in the treatment of malaria and related symptoms were assessed for their antiplasmodial value against the chloroquine sensitive strain of Plasmodium berghei. Crude extracts (200 mg/kg) and chloroquine (5 mg/kg) were administered to different groups of Swiss mice. The percentage of parasitemia, survival time, and haematological parameters were determined. Both extracts significantly (p<0.05) inhibited parasitemia and improved survival time in infected mice. The crude extracts prevented loss of some haematological parameters. A. viridis had a distinct effect on the packed cell volume. The extract was able to protect the liver from some of the damage. This study however showed that the methanolic extracts of A. viridis and L. taraxacifolia possess antiplasmodial activity. The results of this study can be used as a basis for further phytochemical investigations in the search for new and locally affordable antimalarial agents.

scholarly journals Antimalarial Activity of Hydroalcoholic Root Extract of Acanthus polystachyus Delile (Acanthaceae) Against Plasmodium berghei–Infected Mice

2019 ◽  
Vol 24 ◽  
pp. 2515690X1988532 ◽  
Author(s):  
Dagninet Derebe ◽  
Muluken Wubetu
Keyword(s):  
Crude Extract ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
New Drugs ◽  
Root Extract ◽  
Root Extracts ◽  
Antimalarial Agents ◽  
Mean Survival Time

Failure of the efficacy of antimalarial drugs is recognized in different classes of medicines for treating malaria, which urges the need for new drugs. This study tried to check the in vivo antimalarial activity of the root extracts of Acanthus polystachyus Delile against Plasmodium berghei–infected mice. The study revealed that the methanolic crude extract of the root of Acanthus polystachyus Delile showed significant ( P < .01) parasitemia suppressive activities in both models compared with the negative control. Parasitemia suppressive activities were 25.26%, 33.46%, and 51.48% in a 4-day suppressive test and 23.31%, 31.20%, and 43.54% in prophylaxis test at 100, 200, and 400 mg/kg of the extract, respectively, as compared to the negative control. Besides, the extract increases mean survival time significantly in all tested doses in a 4-day suppressive test, but in the prophylaxis model, only mice treated with 200 and 400 mg/kg significantly lived longer. Based on this finding, the root of Acanthus polystachyus Delile has strong antimalarial activity, which may be a good candidate for new antimalarial agents.

scholarly journals Antimalarial Activity of Hydromethanolic Crude Extract and Chloroform Fraction of Brucea antidysenterica Leaves in Plasmodium berghei-Infected Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Tezera Jemere Aragaw ◽  
Kefyalew Ayalew Getahun
Keyword(s):  
Crude Extract ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Chloroform Fraction ◽  
Curative Effect ◽  
Antimalarial Agents ◽  
Different Doses

Background. Different parts of Brucea antidysenterica are used in traditional and alternative medicine in Ethiopia for the treatment of different health problems including malaria and have good in vitro antimalarial activity. However, no in vivo study was conducted to substantiate the claim. Our study planned to determine the antimalarial effect of B. antidysenterica extract. Methods. Swiss albino mice (6–8 weeks old, 20–28 g) were inoculated with Plasmodium berghei. Different doses of both hydromethanolic extract and chloroform fraction were orally given at 100, 200, and 400 mg/kg/day. Results. The parasitemia suppression percent of hydromethanolic crude extract and chloroform fraction in chemosuppressive tests ranged between 33.48 and 75.93% and 38.32 and 76.64%, respectively. The hydromethanolic crude extract and chloroform fraction exhibited the curative effect of 46.75–70.91% and 50.30–80.06% parasitemia suppression, respectively ( p  < 0.001), compared with negative control. Conclusion. From our study, it is concluded that the hydromethanolic crude extract and chloroform fraction of B. antidysenterica leaves showed promising antiplasmodial effects against Plasmodium berghei. This upholds the folkloric use of B. antidysenterica leaves and the thought of as a possible source to develop new antimalarial agents.

scholarly journals In Vivo Antimalarial Activity of the Beta-Carboline Alkaloid Manzamine A

2000 ◽  
Vol 44 (6) ◽  
pp. 1645-1649 ◽  
Author(s):  
Kenny K. H. Ang ◽  
Michael J. Holmes ◽  
Tatsuo Higa ◽  
Mark T. Hamann ◽  
Ursula A. K. Kara
Keyword(s):  
Plasmodium Berghei ◽  
Malaria Parasite ◽  
Antimalarial Activity ◽  
Single Injection ◽  
Morphological Changes ◽  
Rodent Malaria Parasite ◽  
Manzamine A ◽  
Antimalarial Agents ◽  
Single Intraperitoneal Injection

ABSTRACT Manzamine A, a β-carboline alkaloid present in several marine sponge species, inhibits the growth of the rodent malaria parasitePlasmodium berghei in vivo. More than 90% of the asexual erythrocytic stages of P. berghei were inhibited after a single intraperitoneal injection of manzamine A into infected mice. A remarkable aspect of manzamine A treatment is its ability to prolong the survival of highly parasitemic mice, with 40% recovery 60 days after a single injection. Oral administration of an oil suspension of manzamine A also produced significant reductions in parasitemia. The plasma manzamine A concentration peaked 4 h after injection and remained high even at 48 h. Morphological changes of P. berghei were observed 1 h after treatment of infected mice. (−)-8-Hydroxymanzamine A also displayed antimalarial activity, whereas manzamine F, a ketone analog of manzamine A, did not. Our results suggest that manzamine A and (−)-8-hydroxymanzamine A are promising new antimalarial agents.

scholarly journals In Vivo Antiplasmodial Activity of Different Solvent Extracts of Myrianthus libericus Stem Bark and Its Constituents in Plasmodium berghei-Infected Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Michael Kwesi Baah ◽  
Abraham Yeboah Mensah ◽  
Evelyn Asante-Kwatia ◽  
Isaac Kingsley Amponsah ◽  
Arnold Donkor Forkuo ◽  
...  
Keyword(s):  
Weight Loss ◽  
Plasmodium Berghei ◽  
Ethyl Acetate Fraction ◽  
Stem Bark ◽  
Antiplasmodial Activity ◽  
Antimalarial Agent ◽  
Antimalarial Agents ◽  
Hydroethanolic Extract ◽  
First Time

The emergence and resurgence of P. falciparum resistance to generations of antimalarial drugs have prompted the search for new, effective, and safe antimalarial agents. This study aimed at investigating the in vivo antiplasmodial activity of the 70% hydroethanolic extract and constituents of the stem bark of Myrianthus libericus based on its ethnomedicinal use as an antimalarial agent. The antiplasmodial activity was assessed in Swiss albino mice employing the 4-day suppressive and Rane’s tests. MLB significantly (p<0.0001) suppressed parasitaemia by 52.26%, 65.40%, and 77.11% at 50, 100, and 200 mg·kg−1 doses, respectively, in the 4-day suppressive test. In Rane’s test, the highest parasitaemia suppression of 72.50% was recorded at a dose of 200 mg·kg−1 of the extract. Fractionation of the bioactive ethyl acetate fraction by solvent-solvent partitioning and column chromatography led to the isolation of friedelan-3-one and stigmasterol being reported for the first time from this species. The compounds demonstrated remarkable antiplasmodial activity by suppressing parasitaemia by 65–72% in the suppressive test and 61–70% in the curative test at doses of 10–30 mg·kg−1. Both the extract and the isolated compounds significantly prolonged the survival time of infected mice and averted the cardinal signs associated with P. berghei-induced malaria including weight loss, hypothermia, and haemolysis. The results obtained confirm the prospect of M. libericus as an important source of new antimalarial compounds and justifies its folkloric use as an antimalarial agent.

Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Haicheng Liu ◽  
Yushi Futamura ◽  
Honghai Wu ◽  
Aki Ishiyama ◽  
Taotao Zhang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antimalarial Activity ◽  
In Vitro Assays ◽  
Compound Library ◽  
Antimalarial Agents ◽  
Phenotypic Screen ◽  
Ic50 Values ◽  
Substituted Benzamides

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3-cinnamamido-N-substituted benzamides. Method: In this study, a screening of our compound library was carried out against the multidrug-sensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 µM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 µM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, phenotypic screen of our compound library resulted in the first report of 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against P. falciparum 3D7 strain with IC50 values around 0.1 µM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.

scholarly journals Actin and Microtubules Differently Contribute to Vacuolar Targeting Specificity during the Export from the ER

Membranes ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 299
Author(s):  
Monica De Caroli ◽  
Fabrizio Barozzi ◽  
Luciana Renna ◽  
Gabriella Piro ◽  
Gian-Pietro Di Sansebastiano
Keyword(s):  
Spatial Targeting ◽  
Traffic Regulation ◽  
Emergent Features ◽  
Vacuolar Sorting ◽  
Er Export ◽  
Golgi Network ◽  
Relationship Of ◽  
The Relationship ◽  
Fine Tune

Plants rely on both actin and microtubule cytoskeletons to fine-tune sorting and spatial targeting of membranes during cell growth and stress adaptation. Considerable advances have been made in recent years in the comprehension of the relationship between the trans-Golgi network/early endosome (TGN/EE) and cytoskeletons, but studies have mainly focused on the transport to and from the plasma membrane. We address here the relationship of the cytoskeleton with different endoplasmic reticulum (ER) export mechanisms toward vacuoles. These emergent features of the plant endomembrane traffic are explored with an in vivo approach, providing clues on the traffic regulation at different levels beyond known proteins’ functions and interactions. We show how traffic of vacuolar markers, characterized by different vacuolar sorting determinants, diverges at the export from the ER, clearly involving different components of the cytoskeleton.

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