scholarly journals A polyphenol, pyrogallol changes the acidic pH of the digestive vacuole of Plasmodium falciparum

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Nur Saidatul Aqilah Ja’afar ◽  
Nik Nor Imam Nik Mat Zin ◽  
Fatin Sofia Mohamad ◽  
Nurhidanatasha Abu-Bakar
Keyword(s):  
Plasmodium Falciparum ◽  
Proton Pump ◽  
Antimalarial Activity ◽  
Fluorescein Isothiocyanate ◽  
Drug Candidate ◽  
Digestive Vacuole ◽  
Atpase Inhibitor ◽  
Trophozoite Stage ◽  
Concanamycin A ◽  
Ic50 Value

Pyrogallol has a capability of generating free radicals like other antimalarial drugs such as artemisinin, which is thought to inhibit the proton pump located in the membrane of the Plasmodium falciparum digestive vacuole, thus alkalinising this acidic organelle. This study aimed to determine pH changes of the malaria parasite’s digestive vacuole following treatment with pyrogallol. The antimalarial activity of this compound was evaluated by a malarial SYBR Green 1 fluorescence-based assay to determine the 50% inhibitory concentration (IC50). Based on the IC50 value, different concentrations of pyrogallol were selected to ensure changes of the digestive vacuole pH were not due to parasite death. This was measured by flow cytometry after 4-hour pyrogallol treatment on the fluorescein isothiocyanate-dextran-accumulated digestive vacuole of the mid-trophozoite stage parasites. Pyrogallol showed a moderate antimalarial activity with the IC50 of 2.84 ± 9.40 µM. The treatment of 1.42, 2.84 and 5.67 µM pyrogallol increased 2.9, 3.0 and 3.1 units of the digestive vacuole pH, respectively as compared with the untreated parasite (pH 5.6 ± 0.78). The proton pump, V-type H+-ATPase might be inhibited by pyrogallol, hence causing the digestive vacuole pH alteration, which is similar with the result shown by a standard V-type H+-ATPase inhibitor, concanamycin A. This study provides a fundamental understanding on the antimalarial activity and mechanism of action of pyrogallol that has a potential to be the antimalarial drug candidate.

scholarly journals Skrining Aktivitas Antimalaria Beberapa Tanaman Indonesia Hasil Eksplorasi Dari Hutan Raya Cangar, Batu-Malang, Jawa Timur

2017 ◽  
Vol 3 (1) ◽  
pp. 7
Author(s):  
Achmad Fuad Hafid ◽  
Nike Puliansari ◽  
Nur Suci Lestari ◽  
Lidya Tumewu ◽  
Abdul Rahman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Eucalyptus Globulus ◽  
Antimalarial Activity ◽  
Probit Analysis ◽  
National Forest ◽  
Parasitic Disease ◽  
Antimalarial Therapy ◽  
Ic50 Value ◽  
Stem Extract

Background: Malaria is the most important parasitic disease. Malaria control which depends on specific chemotherapy now complicated by resistance of Plasmodium falciparum to most commonly available antimalarial drug. Such situation has heralded the need for alternative antimalarial therapy. Objective: This research aim was to find new antimalarial candidates from some Indonesia plants collected from Cangar National Forest, Batu-Malang, East Java. Methods: Eleven samples of leaves and stem extracts were screened against Plasmodium falciparum 3D7 culture which maintained in RPMI-1640 Medium. Samples tested in concentration of 0.01, 0.1, 1, 10 and 100 µg/ml. Probit analysis was used to determine IC50. Results: In vitro antimalarial activity revealed that only three crude extracts samples from Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract had good antimalarial activity with IC50 value of 0.33, 0.20 and 0.55 µg/ml, respectively. Conclusions: Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract might be a good candidate for antimalarial natural product resources.

scholarly journals Antimalarial activity of ulein and proof of its action on the Plasmodium falciparum digestive vacuole

2010 ◽  
Vol 9 (S2) ◽  
Author(s):  
Alaíde Braga de Oliveira ◽  
Maria Fâni Dolabela ◽  
Marinete Marins Póvoa ◽  
Cid Aimbiré M Santos ◽  
Fernando de Pilla Varotti
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Digestive Vacuole

scholarly journals Synergistic Interactions of the Antiretroviral Protease Inhibitors Saquinavir and Ritonavir with Chloroquine and Mefloquine against Plasmodium falciparum In Vitro

2006 ◽  
Vol 51 (2) ◽  
pp. 759-762 ◽  
Author(s):  
T. S. Skinner-Adams ◽  
K. T. Andrews ◽  
L. Melville ◽  
J. McCarthy ◽  
D. L. Gardiner
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasmodium Falciparum ◽  
Protease Inhibitors ◽  
Antimalarial Activity ◽  
Digestive Vacuole ◽  
Synergistic Interactions ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus ◽  
Pepstatin A

ABSTRACT The antimalarial activity of several antiretroviral protease inhibitor combinations was investigated. Data demonstrate that ritonavir and saquinavir behave synergistically with chloroquine and mefloquine. These data, and interactions with pepstatin-A, E-64, and bestatin, suggest that human immunodeficiency virus protease inhibitors do not target digestive-vacuole plasmepsins.

scholarly journals Mutation in the Plasmodium falciparum CRT Protein Determines the Stereospecific Activity of Antimalarial Cinchona Alkaloids

2012 ◽  
Vol 56 (10) ◽  
pp. 5356-5364 ◽  
Author(s):  
Carol E. Griffin ◽  
Jonathan M. Hoke ◽  
Upeka Samarakoon ◽  
Junhui Duan ◽  
Jianbing Mu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Cinchona Alkaloids ◽  
Chloroquine Resistance ◽  
Digestive Vacuole ◽  
Content Type ◽  
Chloroquine Resistance Transporter ◽  
Clonal Lines

ABSTRACTTheCinchonaalkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (−)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (−)-isomersin vitroandin vivoagainstPlasmodium falciparummalaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparumchloroquine resistance transporter), reversed the normal potency order of quinine and quinidine towardP. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured thein vitrosusceptibility of eight clonal lines ofP. falciparumderived from the 106/1 strain, each containing a uniquepfcrtallele, to fourCinchonastereoisomer pairs: quinine and quinidine; cinchonidine and cinchonine; hydroquinine and hydroquinidine; 9-epiquinine and 9-epiquinidine. Stereospecific potency of theCinchonaalkaloids was associated with changes in charge and hydrophobicity of mutable PfCRT amino acids. In isogenic chloroquine-resistant lines, the IC50ratio of (−)/(+) CA pairs correlated with side chain hydrophobicity of the position 76 residue. Second-site PfCRT mutations negated the K76I stereospecific effects: charge-change mutations C72R or Q352K/R restored potency patterns similar to the parent K76 line, while V369F increased susceptibility to the alkaloids and nullified stereospecific differences between alkaloid pairs. Interactions between key residues of the PfCRT channel/transporter with (−) and (+) alkaloids are stereospecifically determined, suggesting that PfCRT binding plays an important role in the antimalarial activity of quinine and otherCinchonaalkaloids.

scholarly journals Aktivitas Penghambatan Ekstrak Etanol Daun Cassia Spectabilis Terhadap Pertumbuhan Plasmodium falciparum dan Plasmodium berghei

2017 ◽  
Vol 3 (1) ◽  
pp. 17 ◽  
Author(s):  
Wiwied Ekasari ◽  
Nindya Tresiana ◽  
Suciati Iryani ◽  
Tutik Sri Wahyuni ◽  
Heny Arwaty
Keyword(s):  
Plasmodium Falciparum ◽  
Methanol Extract ◽  
Antimalarial Activity ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
In Vivo Test ◽  
Ic50 Value ◽  
Cassia Spectabilis

Background: Antimalarial screening against nine species of the genus Cassia showed that the methanol extract of leaves Cassia spectabilis have the highest activity. Since it will be used as a traditional medicine, hence it is needed further studies of antimalarial activity of these plants by choosing a safer solvent, namely ethanol. Objective: In vitro anti-malarial activity against Plasmodium falciparum was conducted using the method of Trager and Jensen. Methods: The serial solution tested were: 100, 10, 1,  0.1 and 0.01 µg/ mL, while the in vivo test was performed based on Peter’s test (The days suppressive test) that using P. berghei (strain ANKA) infected mice. Results: The results showed that ethanolic extract of C. spectabilis leaves has inhibitory activity against P. falciparum with IC50 value of 12.52 µg/ mL and against P. berghei with ED50 value of 131.5 mg/kg body weight. Conclusions: A further study to see the potential of ethanol extract from C. Spectabilis leaves as anti-malaria is warranted. 

scholarly journals Defining the Timing of Action of Antimalarial Drugs against Plasmodium falciparum

2013 ◽  
Vol 57 (3) ◽  
pp. 1455-1467 ◽  
Author(s):  
Danny W. Wilson ◽  
Christine Langer ◽  
Christopher D. Goodman ◽  
Geoffrey I. McFadden ◽  
James G. Beeson
Keyword(s):  
Flow Cytometry ◽  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Antimalarial Activity ◽  
Trichostatin A ◽  
Mechanisms Of Action ◽  
Trophozoite Stage ◽  
Merozoite Invasion ◽  
Content Type

ABSTRACTMost current antimalarials for treatment of clinicalPlasmodium falciparummalaria fall into two broad drug families and target the food vacuole of the trophozoite stage. No antimalarials have been shown to target the brief extracellular merozoite form of blood-stage malaria. We studied a panel of 12 drugs, 10 of which have been used extensively clinically, for their invasion, schizont rupture, and growth-inhibitory activity using high-throughput flow cytometry and new approaches for the study of merozoite invasion and early intraerythrocytic development. Not surprisingly, given reported mechanisms of action, none of the drugs inhibited merozoite invasionin vitro. Pretreatment of erythrocytes with drugs suggested that halofantrine, lumefantrine, piperaquine, amodiaquine, and mefloquine diffuse into and remain within the erythrocyte and inhibit downstream growth of parasites. Studying the inhibitory activity of the drugs on intraerythrocytic development, schizont rupture, and reinvasion enabled several different inhibitory phenotypes to be defined. All drugs inhibited parasite replication when added at ring stages, but only artesunate, artemisinin, cycloheximide, and trichostatin A appeared to have substantial activity against ring stages, whereas the other drugs acted later during intraerythrocytic development. When drugs were added to late schizonts, only artemisinin, cycloheximide, and trichostatin A were able to inhibit rupture and subsequent replication. Flow cytometry proved valuable forin vitroassays of antimalarial activity, with the free merozoite population acting as a clear marker for parasite growth inhibition. These studies have important implications for further understanding the mechanisms of action of antimalarials, studying and evaluating drug resistance, and developing new antimalarials.

scholarly journals Aktivitas Penghambatan Ekstrak Etanol Daun Cassia Spectabilis Terhadap Pertumbuhan Plasmodium falciparum dan Plasmodium berghei

2017 ◽  
Vol 3 (1) ◽  
pp. 17
Author(s):  
Wiwied Ekasari ◽  
Nindya Tresiana ◽  
Suciati Iryani ◽  
Tutik Sri Wahyuni ◽  
Heny Arwaty
Keyword(s):  
Plasmodium Falciparum ◽  
Methanol Extract ◽  
Antimalarial Activity ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
In Vivo Test ◽  
Ic50 Value ◽  
Cassia Spectabilis

Background: Antimalarial screening against nine species of the genus Cassia showed that the methanol extract of leaves Cassia spectabilis have the highest activity. Since it will be used as a traditional medicine, hence it is needed further studies of antimalarial activity of these plants by choosing a safer solvent, namely ethanol. Objective: In vitro anti-malarial activity against Plasmodium falciparum was conducted using the method of Trager and Jensen. Methods: The serial solution tested were: 100, 10, 1,  0.1 and 0.01 µg/ mL, while the in vivo test was performed based on Peter’s test (The days suppressive test) that using P. berghei (strain ANKA) infected mice. Results: The results showed that ethanolic extract of C. spectabilis leaves has inhibitory activity against P. falciparum with IC50 value of 12.52 µg/ mL and against P. berghei with ED50 value of 131.5 mg/kg body weight. Conclusions: A further study to see the potential of ethanol extract from C. Spectabilis leaves as anti-malaria is warranted. 

scholarly journals In Vitro Antimalarial Activity and Toxicity of Helianthus annuus L. Leaf Extract against Plasmodium falciparum

2021 ◽  
Vol 8 (3) ◽  
pp. 259
Author(s):  
Nuriha Marangoh ◽  
Suciati Suciati ◽  
Wiwied Ekasari
Keyword(s):  
Plasmodium Falciparum ◽  
Helianthus Annuus ◽  
Antimalarial Activity ◽  
Chloroform Extract ◽  
Morbidity Rate ◽  
Cytotoxicity Test ◽  
Leaf Extracts ◽  
Helianthus Annuus L ◽  
Falciparum Strain ◽  
Ic50 Value

Background: Malaria is one of the public health problems in Indonesia. The morbidity rate is still quite high, especially in the eastern part of Indonesia. Objective: This study aimed to determine the inhibitory activity of the leaf extracts of Helianthus annuus L. against Plasmodium falciparum strain 3D7 as well as the cytotoxicity of the extracts. Methods: The leaves of H. annuus were extracted by the maceration method with n-hexane, chloroform, and ethanol 96% to increase polarity. The antimalarial assay was performed by using Trager and Jensen method, and the cytotoxicity test was carried out by the MTT method. Results: The results of antimalarial study showed that the chloroform extract had IC50 value of 0.002 µg/mL and CC50value of 138.03 µg/mL, 96% ethanol extract had an IC50 value of 0.02 µg/mL and CC50 value of 617.81 µg/mL, and n-hexane extract had an IC50 value of 1.29 µg/mL and CC50 value of 104.89 µg/mL. The selectivity index (SI) values of the chloroform, ethanolic, and n-hexane extracts were calculated and obtained 69,015.00, 30,890.50, and 81.31, respectively. Conclusion:  To conclude, the chloroform extract of H. annuus L. leaf gave strong antimalarial activity against P. falciparum strain 3D7 without any cytotoxicity; therefore, H. annuus L. leaf can be a good candidate for the development of an antimalarial drug.

scholarly journals Phytochemical, Biological and Computational Investigations of Erythrina fusca Lour. to Assess Antimalarial Property against Plasmodium falciparum

2020 ◽  
Author(s):  
Saiful Arefeen Sazed ◽  
Ohedul Islam ◽  
Sarah L. Bliese ◽  
Muhammad Riadul Haque Hossainey ◽  
Mahfuza Afroz Soma ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Antimalarial Drug ◽  
Antimalarial Activity ◽  
Drug Candidate ◽  
Separation And Purification ◽  
Membrane Stabilization ◽  
Phytochemical Investigation ◽  
Biological Tests

For centuries medicinal plants have been traditionally used for prophylaxis and ailment of diseases. Nowadays it’s easy to isolate, purify, and characterize bioactive compounds with high efficacy. To investigate the medicinal especially antimalarial property of traditionally used plants, a number of Erythrina spp have been reviewed systematically where Erythrina fusca has been selected for further analysis. Phytochemical investigation included chromatographic separation and purification of compounds followed by characterization using NMR. In-vitro antimalarial drug sensitivity ELISA was carried out against chloroquine (CQ) sensitive 3D7 and resistant Dd2 strains. Additional biological tests such as central and peripheral analgesic, antioxidant, anti-diarrheal, hypoglycemic, thrombolytic, and membrane stabilization activities were also investigated. Molecular docking was performed using the isolated compounds against clinically important 14 Plasmodium falciparum proteins. For the first time, Phaseolin, Phytol, β-amyrin, Lupeol, and Stigmasterol are reported here and extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC50 4.94-22 µg/mL). Potent central analgesic, antioxidant and anti-diarrheal activities (p<0.05) and mild thrombolytic and membrane stabilization properties were also observed. Molecular docking of Phaseolin bolsters its potential as a new antimalarial drug candidate. This study projects significant medicinal values and necessitates further investigations to reveal its potential as a novel source of therapeutics.

scholarly journals Skrining Aktivitas Antimalaria Beberapa Tanaman Indonesia Hasil Eksplorasi Dari Hutan Raya Cangar, Batu-Malang, Jawa Timur

2017 ◽  
Vol 3 (1) ◽  
pp. 7
Author(s):  
Achmad Fuad Hafid ◽  
Nike Puliansari ◽  
Nur Suci Lestari ◽  
Lidya Tumewu ◽  
Abdul Rahman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Eucalyptus Globulus ◽  
Antimalarial Activity ◽  
Probit Analysis ◽  
National Forest ◽  
Parasitic Disease ◽  
Antimalarial Therapy ◽  
Ic50 Value ◽  
Stem Extract

Background: Malaria is the most important parasitic disease. Malaria control which depends on specific chemotherapy now complicated by resistance of Plasmodium falciparum to most commonly available antimalarial drug. Such situation has heralded the need for alternative antimalarial therapy. Objective: This research aim was to find new antimalarial candidates from some Indonesia plants collected from Cangar National Forest, Batu-Malang, East Java. Methods: Eleven samples of leaves and stem extracts were screened against Plasmodium falciparum 3D7 culture which maintained in RPMI-1640 Medium. Samples tested in concentration of 0.01, 0.1, 1, 10 and 100 µg/ml. Probit analysis was used to determine IC50. Results: In vitro antimalarial activity revealed that only three crude extracts samples from Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract had good antimalarial activity with IC50 value of 0.33, 0.20 and 0.55 µg/ml, respectively. Conclusions: Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract might be a good candidate for antimalarial natural product resources.

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