scholarly journals In Vitro and In Vivo Properties of Ellagic Acid in Malaria Treatment

2008 ◽  
Vol 53 (3) ◽  
pp. 1100-1106 ◽  
Author(s):  
Patrice Njomnang Soh ◽  
Benoît Witkowski ◽  
David Olagnier ◽  
Marie-Laure Nicolau ◽  
Maria-Concepcion Garcia-Alvarez ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Ellagic Acid ◽  
Antimalarial Activity ◽  
Inhibitory Effect ◽  
Oral Route ◽  
Mechanisms Of Action ◽  
The World ◽  
Erythrocytic Cycle

ABSTRACT Malaria is one of the most significant causes of infectious disease in the world. The search for new antimalarial chemotherapies has become increasingly urgent due to the parasites’ resistance to current drugs. Ellagic acid is a polyphenol found in various plant products. In this study, antimalarial properties of ellagic acid were explored. The results obtained have shown high activity in vitro against all Plasmodium falciparum strains whatever their levels of chloroquine and mefloquine resistance (50% inhibitory concentrations ranging from 105 to 330 nM). Ellagic acid was also active in vivo against Plamodium vinckei petteri in suppressive, curative, and prophylactic murine tests, without any toxicity (50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day). The study of the point of action of its antimalarial activity in the erythrocytic cycle of Plasmodium falciparum demonstrated that it occurred at the mature trophozoite and young schizont stages. Moreover, ellagic acid has been shown to potentiate the activity of current antimalarial drugs such as chloroquine, mefloquine, artesunate, and atovaquone. This study also proved the antioxidant activity of ellagic acid and, in contrast, the inhibitory effect of the antioxidant compound N-acetyl-l-cysteine on its antimalarial efficacy. The possible mechanisms of action of ellagic acid on P. falciparum are discussed in light of the results. Ellagic acid has in vivo activity against plasmodia, but modification of the compound could lead to improved pharmacological properties, principally for the oral route.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

Synthesis and antimalarial activity of novel bicyclic and tricyclic aza-peroxides

RSC Advances ◽  
2016 ◽  
Vol 6 (28) ◽  
pp. 23718-23725 ◽  
Author(s):  
Lalit Yadav ◽  
Mohit K. Tiwari ◽  
Bharti Rajesh Kumar Shyamlal ◽  
Manas Mathur ◽  
Ajit K. Swami ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Oral Route ◽  
Plasmodium Yoelii ◽  
Swiss Mice

Bicyclic and tricyclic aza-peroxides were synthesized and assessed for theirin vitroandin vivoantimalarial activities againstPlasmodium falciparum(3D7 strain) andPlasmodium yoelii nigeriensisin Swiss mice by an oral route, respectively.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals Overexpression of Plasmodium falciparum M1 Aminopeptidase Promotes an Increase in Intracellular Proteolysis and Modifies the Asexual Erythrocytic Cycle Development

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1452
Author(s):  
Carolina C. Hoff ◽  
Mauro F. Azevedo ◽  
Adriana B. Thurler ◽  
Sarah El Chamy Maluf ◽  
Pollyana M. S. Melo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Fold Increase ◽  
Cysteine Proteases ◽  
Aminopeptidase Activity ◽  
Lower Sensitivity ◽  
Wild Type ◽  
Erythrocytic Cycle ◽  
Transgenic Parasite

Plasmodium falciparum, the most virulent of the human malaria parasite, is responsible for high mortality rates worldwide. We studied the M1 alanyl-aminopeptidase of this protozoan (PfA-M1), which is involved in the final stages of hemoglobin cleavage, an essential process for parasite survival. Aiming to help in the rational development of drugs against this target, we developed a new strain of P. falciparum overexpressing PfA-M1 without the signal peptide (overPfA-M1). The overPfA-M1 parasites showed a 2.5-fold increase in proteolytic activity toward the fluorogenic substrate alanyl-7-amido-4-methylcoumarin, in relation to the wild-type group. Inhibition studies showed that overPfA-M1 presented a lower sensitivity against the metalloaminopeptidase inhibitor bestatin and to other recombinant PfA-M1 inhibitors, in comparison with the wild-type strain, indicating that PfA-M1 is a target for the in vitro antimalarial activity of these compounds. Moreover, overPfA-M1 parasites present a decreased in vitro growth, showing a reduced number of merozoites per schizont, and also a decrease in the iRBC area occupied by the parasite in trophozoite and schizont forms when compared to the controls. Interestingly, the transgenic parasite displays an increase in the aminopeptidase activity toward Met-, Ala-, Leu- and Arg-7-amido-4-methylcoumarin. We also investigated the potential role of calmodulin and cysteine proteases in PfA-M1 activity. Taken together, our data show that the overexpression of PfA-M1 in the parasite cytosol can be a suitable tool for the screening of antimalarials in specific high-throughput assays and may be used for the identification of intracellular molecular partners that modulate their activity in P. falciparum.

scholarly journals Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice

2009 ◽  
Vol 105 (1) ◽  
pp. 275-279 ◽  
Author(s):  
Matheus Santos de Sá ◽  
José Fernando Oliveira Costa ◽  
Antoniana Ursine Krettli ◽  
Mariano Gustavo Zalis ◽  
Gabriela Lemos de Azevedo Maia ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Betulinic Acid ◽  
Antimalarial Activity

scholarly journals Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Letícia Tiburcio Ferreira ◽  
Juliana Rodrigues ◽  
Gustavo Capatti Cassiano ◽  
Tatyana Almeida Tavella ◽  
Kaira Cristina Peralis Tomaz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
Antimalarial Activity ◽  
Drug Repositioning ◽  
Dna Gyrase ◽  
Plasmodium Yoelii ◽  
Computer Assisted ◽  
Content Type

ABSTRACT Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks, and time-to-market. Herein, we have used this strategy to identify novel antimalarial hits. We used a comparative in silico chemogenomics approach to select Plasmodium falciparum and Plasmodium vivax proteins as potential drug targets and analyzed them using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity. Among the seven drugs identified as promising antimalarial candidates, the anthracycline epirubicin was selected for further experimental validation. Epirubicin was shown to be potent in vitro against sensitive and multidrug-resistant P. falciparum strains and P. vivax field isolates in the nanomolar range, as well as being effective against an in vivo murine model of Plasmodium yoelii. Transmission-blocking activity was observed for epirubicin in vitro and in vivo. Finally, using yeast-based haploinsufficiency chemical genomic profiling, we aimed to get insights into the mechanism of action of epirubicin. Beyond the target predicted in silico (a DNA gyrase in the apicoplast), functional assays suggested a GlcNac-1-P-transferase (GPT) enzyme as a potential target. Docking calculations predicted the binding mode of epirubicin with DNA gyrase and GPT proteins. Epirubicin is originally an antitumoral agent and presents associated toxicity. However, its antiplasmodial activity against not only P. falciparum but also P. vivax in different stages of the parasite life cycle supports the use of this drug as a scaffold for hit-to-lead optimization in malaria drug discovery.

scholarly journals Antiplasmodial Quinones from the Rhizomes of Kniphofia Foliosa

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Martha Induli ◽  
Meron Gebru ◽  
Negera Abdissa ◽  
Hosea Akala ◽  
Ingrid Wekesa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Methyl Ether ◽  
Spectroscopic Data ◽  
Antimalarial Activity ◽  
In Vivo Assay

Extracts of the rhizomes of Kniphofia foliosa exhibited antiplasmodial activities against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3–5 μg/mL. A phenyloxanthrone, named 10-acetonylknipholone cyclooxanthrone (1) and an anthraquinone-anthrone dimer, chryslandicin 10-methyl ether (2), were isolated from the rhizomes, along with known quinones, including the rare phenylanthraquinone dimers, joziknipholones A and B. The structures of these compounds were determined based on spectroscopic data. This is the second report on the occurrence of the dimeric phenylanthraquinones in nature. In an in vitro antiplasmodial assay of the isolated compounds, activity was observed for phenylanthraquinones, anthraquinone-anthrone dimers and dimeric phenylanthraquinones, with joziknipholone A being the most active. The new compound, 10-acetonylknipholone cyclooxanthrone, also showed anti-plasmodial activity. In an in vivo assay, knipholone anthrone displayed marginal antimalarial activity.

Antimalarial Activity of Phenazines from Lapachol, β-Lapachone and Its Derivatives Against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.

ChemInform ◽  
2004 ◽  
Vol 35 (26) ◽  
Author(s):  
Valter F. de Andrade-Neto ◽  
Marilia O. F. Goulart ◽  
Jorge F. da Silva Filho ◽  
Matuzalem J. da Silva ◽  
Maria do Carmo F. R. Pinto ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Antimalarial Activity

Hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug‐resistant Plasmodium falciparum

2019 ◽  
Vol 40 (3) ◽  
pp. 931-971 ◽  
Author(s):  
Lian‐Shun Feng ◽  
Zhi Xu ◽  
Le Chang ◽  
Chuan Li ◽  
Xiao‐Fei Yan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Drug Resistant ◽  
Hybrid Molecules

scholarly journals Andrographolide: A Novel Antimalarial Diterpene Lactone Compound fromAndrographis paniculataand Its Interaction with Curcumin and Artesunate

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Kirti Mishra ◽  
Aditya P. Dash ◽  
Nrisingha Dey
Keyword(s):  
Plasmodium Falciparum ◽  
Life Span ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Andrographis Paniculata ◽  
Antiplasmodial Activity ◽  
Template Molecule

Andrographolide (AND), the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plantAndrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages ofPlasmodium falciparum in vitroandPlasmodium bergheiANKAin vivo. IC50s for artesunate (AS), andrographolide (AND), and curcumin (CUR) were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND) was found synergistic with curcumin (CUR) and addictively interactive with artesunate (AS).In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%), compared to the control (81%), but also by extending the life span by 2-3 folds. Being nontoxic to thein vivosystem this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

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