Brine shrimp toxicity and invitro antimalarial activity of Citrus aurantifolia (Christm.) Swingle against Plasmodium falciparum 3D7

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.

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In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2094 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2094-2098 ◽

Cited By ~ 13

Author(s):

B Pradines ◽

F Ramiandrasoa ◽

L K Basco ◽

L Bricard ◽

G Kunesch ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Mechanism Of Action ◽

Ribonucleotide Reductase ◽

Antimalarial Activity ◽

Iron Chelators ◽

Resistant Clone ◽

Iron Deprivation ◽

Level Of Activity ◽

Susceptible Clone

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.

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Synthesis and in Vitro Antimalarial Activity of Alkyl Esters Gallate as a Growth Inhibitors of Plasmodium Falciparum

Oriental Journal Of Chemistry ◽

10.13005/ojc/340207 ◽

2018 ◽

Vol 34 (2) ◽

pp. 655-662 ◽

Cited By ~ 2

Author(s):

Ade Arsianti ◽

Hendry Astuti ◽

Fadilah Fadilah ◽

Daniel Martin Simadibrata ◽

Zoya Marie Adyasa ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Growth Inhibitors ◽

Alkyl Esters

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Multiple Antibiotics Exert Delayed Effects against the Plasmodium falciparum Apicoplast

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00527-07 ◽

2007 ◽

Vol 51 (10) ◽

pp. 3485-3490 ◽

Cited By ~ 184

Author(s):

Erica L. Dahl ◽

Philip J. Rosenthal

Keyword(s):

Plasmodium Falciparum ◽

Cell Division ◽

Antimalarial Activity ◽

Mechanisms Of Action ◽

Malaria Parasites ◽

Delayed Effects ◽

Delayed Death ◽

Antimalarial Action ◽

Multiple Antibiotics

ABSTRACT Several classes of antibiotics exert antimalarial activity. The mechanisms of action of antibiotics against malaria parasites have been unclear, and prior studies have led to conflicting results, in part because they studied antibiotics at suprapharmacological concentrations. We examined the antimalarial effects of azithromycin, ciprofloxacin, clindamycin, doxycycline, and rifampin against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) Plasmodium falciparum strains. At clinically relevant concentrations, rifampin killed parasites quickly, preventing them from initiating cell division. In contrast, pharmacological concentrations of azithromycin, ciprofloxacin, clindamycin, and doxycycline were relatively inactive against parasites initially but exerted a delayed death effect, in which the progeny of treated parasites failed to complete erythrocytic development. The drugs that caused delayed death did not alter the distribution of apicoplasts into developing progeny. However, the apicoplasts inherited by the progeny of treated parasites were abnormal. The loss of apicoplast function became apparent as the progeny of antibiotic-treated parasites initiated cell division, with the failure of schizonts to fully mature or for erythrocyte rupture to take place. These findings explain the slow antimalarial action of multiple antibiotics.

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Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i4.24532 ◽

2015 ◽

Vol 10 (4) ◽

pp. 917 ◽

Cited By ~ 1

Author(s):

Mukesh Kumar Kumawat ◽

Dipak Chetia

Keyword(s):

Plasmodium Falciparum ◽

Molecular Docking ◽

Resistant Strain ◽

Antimalarial Activity ◽

Binding Pocket ◽

Docking Studies ◽

Spectroscopic Techniques ◽

Molecular Docking Studies ◽

Activity Screening

Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of Plasmodium falciparum (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.

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Study on Phytochemical, Antibacterial, Antioxidant and Toxicity Profile of Viscum album Linn Associated with Acacia catechu

Nepal Journal of Biotechnology ◽

10.3126/njb.v3i1.14234 ◽

2015 ◽

Vol 3 (1) ◽

pp. 60-65

Author(s):

Meena Kusi ◽

Kanti Shrestha ◽

Rajani Malla

Keyword(s):

Brine Shrimp ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Viscum Album ◽

Biologically Active ◽

Frap Assay ◽

Antioxidant Power ◽

Percolation Method ◽

Brine Shrimp Toxicity ◽

Acacia Catechu

This study focuses on antibacterial, antioxidant and toxic potentials of Viscum album Linn, commonly known as European mistletoe associated with Acacia catechu (Khayer in Nepali). Methanol extract of the aerial parts of the Mistletoe was prepared by cold percolation method. The resulting extract was simultaneously subjected to phytochemical screening; anti-microbial activity; anti-oxidant potential and Brine shrimp toxicity test. The major biologically active phyto-constituents observed were alkaloids, glycosides, saponins, polyphenols, flavonoids, tannins, terpenoids and cardiac glycosides. Upon antibacterial activity screening, the plant extract was found to be highly effective against Pseudomonas aeruginosa with the zone of inhibition 16±1mm compared to 17±1mm of chloramphenicol (50 mcg). The antioxidant activity as EC50 value by DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity was found to be 1.58 mg/ml while the ferric reducing capacity was measured to be 282.83±19.55 mg FeSO4.7H2O eqvt/g dry wt. of the extract during Ferric Ion Reducing Antioxidant Power (FRAP) Assay. The LC50 value for Brine Shrimp Toxicity Assay was found to be 31.62 ppm. This study shows the medicinal value of the mistletoe associated with Acacia catechu. Further meticulous analysis of this plant might lead to identification of active biomolecules effective as drugs for various ailmentsNepal Journal of Biotechnology. Dec. 2015 Vol. 3, No. 1: 60-65

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Small-molecule histone methyltransferase inhibitors display rapid antimalarial activity against all blood stage forms in Plasmodium falciparum

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1205414109 ◽

2012 ◽

Vol 109 (41) ◽

pp. 16708-16713 ◽

Cited By ~ 89

Author(s):

N. A. Malmquist ◽

T. A. Moss ◽

S. Mecheri ◽

A. Scherf ◽

M. J. Fuchter

Keyword(s):

Plasmodium Falciparum ◽

Small Molecule ◽

Antimalarial Activity ◽

Histone Methyltransferase ◽

Blood Stage

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

Pathogens ◽

10.3390/pathogens10111452 ◽

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.

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