scholarly journals Potentiation of the antimalarial agent rufigallol.

1996 ◽  
Vol 40 (6) ◽  
pp. 1408-1411 ◽  
Author(s):  
R W Winter ◽  
K A Cornell ◽  
L L Johnson ◽  
M Ignatushchenko ◽  
D J Hinrichs ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Oxygen Radicals ◽  
Synergistic Effects ◽  
Compound A ◽  
Similar Compound ◽  
Antimalarial Agent

We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine-resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar analysis was approximately 60-fold for experiments initiated with asynchronous parasites. The most pronounced synergism was observed in experiments with synchronized trophozoite-infected erythrocytes, in which the degree of synergy was at least 300-fold. While the mechanism underlying this drug potentiation remains unresolved, it is hypothesized that rufigallol acts in pro-oxidant fashion to produce oxygen radicals inside parasitized erythrocytes. These radicals would attack exifone, thereby initiating its transformation into a more potent compound, a xanthone.

scholarly journals In vitro activities of the biguanide PS-15 and its metabolite, WR99210, against cycloguanil-resistant Plasmodium falciparum isolates from Thailand.

1997 ◽  
Vol 41 (10) ◽  
pp. 2300-2301 ◽  
Author(s):  
M D Edstein ◽  
S Bahr ◽  
B Kotecka ◽  
G D Shanks ◽  
K H Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Active Metabolite ◽  
Multidrug Resistant ◽  
Antimalarial Agent ◽  
The Mean

The in vitro activities of the new biguanide PS-15 and its putative active metabolite, WR99210, were determined against seven different isolates or clones of Plasmodium falciparum. The mean 50% inhibitory concentrations of PS-15 and WR99210 were 1,015 and 0.06 ng/ml, respectively. WR99210 was up to 363 times more potent than cycloguanil, the active metabolite of proguanil, against cycloguanil-resistant parasites. The pronounced activity of WR99210 against multidrug-resistant P. falciparum indicates that further studies are required to determine the value of the prodrug, PS-15, as an antimalarial agent.

scholarly journals Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yvonne Azasi ◽  
Shannon K. Gallagher ◽  
Ababacar Diouf ◽  
Rebecca A. Dabbs ◽  
Jing Jin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Synergistic Effects

scholarly journals Various Parts of Helianthus annuus Plants as New Sources of Antimalarial Drugs

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Wiwied Ekasari ◽  
Dwi Widya Pratiwi ◽  
Zelmira Amanda ◽  
Suciati ◽  
Aty Widyawaruyanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Helianthus Annuus ◽  
Antimalarial Activity ◽  
Ethanol Extract ◽  
The Other ◽  
Antimalarial Agent ◽  
A Value ◽  
Ethanol Extracts

Background. Each part of H. annuus plants is traditionally used as medicinal remedies for several diseases, including malaria. Antimalarial activity of the leaf and the seed has already been observed; however, there is no report about antimalarial activity of the other parts of H. annuus plants. In this study, we assess in vitro and in vivo antimalarial activity of each part of the plants and its mechanism as antimalarial agent against inhibition of heme detoxification. Objective. To investigate the antimalarial activity of various parts of H. annuus. Methods. Various parts of the H. annuus plant were tested for in vitro antimalarial activity against Plasmodium falciparum 3D7 strain (chloroquine-sensitive), in vivo antimalarial activity against P. berghei using Peters’ 4-day suppressive test in BALB/c mice, curative and prophylaxis assay, and inhibition of heme detoxification by evaluating β-hematin level. Results. Ethanol extract of the roots showed the highest antimalarial activity, followed by ethanol extract of leaves, with IC50 values of 2.3 ± 1.4 and 4.3 ± 2.2 μg/mL, respectively and the percentage inhibition of P. berghei of 63.6 ± 8.0 and 59.3 ± 13.2 at a dose of 100 mg/kg, respectively. Ethanol extract of roots produced an ED50 value of 10.6 ± 0.2 mg/kg in the curative test and showed an inhibition of 79.2% at a dose of 400 mg/kg in the prophylactic assay. In inhibition of heme detoxification assay, root and leaf ethanol extracts yielded a lower IC50 value than positive (chloroquine) control with a value of 0.4 ± 0.0 and 0.5 ± 0.0 mg/mL, respectively. Conclusion. There were promising results of the ethanol extracts of root of H. annuus as a new source for the development of a new plant-based antimalarial agent.

scholarly journals Bisbenzylisoquinolines as modulators of chloroquine resistance in Plasmodium falciparum and multidrug resistance in tumor cells.

1996 ◽  
Vol 40 (6) ◽  
pp. 1476-1481 ◽  
Author(s):  
F Frappier ◽  
A Jossang ◽  
J Soudon ◽  
F Calvo ◽  
P Rasoanaivo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Tumor Cells ◽  
Synergistic Effects ◽  
Cancer Cell Line ◽  
Multidrug Resistant ◽  
Chloroquine Resistance ◽  
Naturally Occurring ◽  
Structure Activity

Ten naturally occurring bisbenzylisoquinolines (BBIQ) and two dihydro derivatives belonging to five BBIQ subgroups were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance to chloroquine of strain FcB1. The same alkaloids were also assessed in vitro for their potentiating activity against vinblastine with the multidrug-resistant clone CCRF-CEM/VLB, established from lymphoblastic acute leukemia. Three of the BBIQ tested had 50% inhibitory concentrations of less than 1 microM. The most potent antimalarial agent was cocsoline (50% inhibitory concentration, 0.22 microM). Regarding the chloroquine-potentiating effect, fangchinoline exhibited the highest biological activity whereas the remaining compounds displayed either antagonistic or slight synergistic effects. Against the multidrug-resistant cancer cell line, fangchinoline was also by far the most active compound. Although there were clear differences between the activities of tested alkaloids, no relevant structure-activity relationship could be established. Nevertheless, fangchinoline appears to be a new biochemical tool able to help in the comprehension of the mechanism of both chloroquine resistance in P. falciparum and multidrug resistance in tumor cells.

On the mode of action of phlorizin as an antimalarial agent in in vitro cultures of plasmodium falciparum

1987 ◽  
Vol 36 (1) ◽  
pp. 123-129 ◽  
Author(s):  
Shirley Kutner ◽  
William V. Breuer ◽  
Hagai Ginsburg ◽  
Z.Ioav Cabantchik
Keyword(s):  
Plasmodium Falciparum ◽  
Mode Of Action ◽  
In Vitro Cultures ◽  
Antimalarial Agent

scholarly journals Isolation of bioactive compounds from medicinal plants used in traditional medicine: Rautandiol B, a potential lead compound against Plasmodium falciparum

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christiana J. Dawurung ◽  
Minh T. H. Nguyen ◽  
Jutharat Pengon ◽  
Kanchana Dokladda ◽  
Ratchanu Bunyong ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Synergistic Effects ◽  
In Vitro Models ◽  
Lead Compound ◽  
Crude Extracts ◽  
Inhibitory Activities ◽  
Phytochemical Components

Abstract Background Neorautanenia mitis, Hydnora abyssinica, and Senna surattensis are medicinal plants with a variety of traditional uses. In this study, we sought to isolate the bioactive compounds responsible for some of these activities, and to uncover their other potential medicinal properties. Methods The DCM and ethanol extracts of the roots of N. mitis and H. abyssinica, and the leaves of S. surattensis were prepared and their phytochemical components were isolated and purified using chromatographic methods. These extracts and their pure phytochemical components were evaluated in in-vitro models for their inhibitory activities against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Mycobacterium tuberculosis, α-amylase (AA), and α-glucosidase (AG). Results Rautandiol B had significant inhibitory activities against two strains of Plasmodium falciparum showing a high safety ratio (SR) and IC50 values of 0.40 ± 0.07 μM (SR - 108) and 0.74 ± 0.29 μM (SR - 133) against TM4/8.2 and K1CB1, respectively. While (−)-2-isopentenyl-3-hydroxy-8-9-methylenedioxypterocarpan showed the highest inhibitory activity against T. brucei rhodesiense with an IC50 value of 4.87 ± 0.49 μM (SR > 5.83). All crude extracts showed inhibitory activities against AA and AG, with three of the most active phytochemical components; rautandiol A, catechin, and dolineon, having only modest activities against AG with IC50 values of 0.28 mM, 0.36 mM and 0.66 mM, respectively. Conclusion These studies have led to the identification of lead compounds with potential for future drug development, including Rautandiol B, as a potential lead compound against Plasmodium falciparum. The relatively higher inhibitory activities of the crude extracts against AG and AA over their isolated components could be due to the synergistic effects between their phytochemical components. These crude extracts could potentially serve as alternative inhibitors of AG and AA and as therapeutics for diabetes.

scholarly journals Ligands of the Peripheral Benzodiazepine Receptor Are Potent Inhibitors of Plasmodium falciparum and Toxoplasma gondii In Vitro

2002 ◽  
Vol 46 (10) ◽  
pp. 3197-3207 ◽  
Author(s):  
Florence Dzierszinski ◽  
Alexandra Coppin ◽  
Marlene Mortuaire ◽  
Etienne Dewailly ◽  
Christian Slomianny ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Toxoplasma Gondii ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor ◽  
Parasite Resistance ◽  
Antimalarial Agents ◽  
Parasite Replication

ABSTRACT The increase in resistance of the malaria parasite Plasmodium falciparum to currently available drugs demands the development of new antimalarial agents. In this quest, we have found that ligands to the peripheral benzodiazepine receptor such as flurazepam, an agonist of the benzodiazepine family, and PK11195, an antagonist derived from isoquinoline, were active against Plasmodium falciparum. These two compounds effectively and rapidly inhibited parasite growth in vitro, irrespective of parasite resistance to chloroquine and mefloquine. Treatment with both drugs induced a sharp and consistent decline in parasitemia, a complete inhibition of parasite replication, and the destruction of parasites within the host red blood cells. Using electron microscopy, we showed that dramatic morphological changes, involving swollen endoplasmic reticulum and the reduction of hemozoin, were consistent with parasite death. The potent activities of flurazepam and PK11195 were also evaluated for antagonist or synergistic effects with currently used antimalarial drugs such as chloroquine and mefloquine. Moreover, flurazepam was found to be active against Toxoplasma gondii, another member of the phylum Apicomplexa. Taken together, our results indicated that benzodiazepines could be considered promising candidates in the treatment of both malaria and toxoplasmosis.

scholarly journals Inhibitory Activity and Docking Analysis of Antimalarial Agents from Stemona sp. toward Ferredoxin-NADP+ Reductase from Malaria Parasites

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Pratiwi Pudjiastuti ◽  
Ni Nyoman T. Puspaningsih ◽  
Imam Siswanto ◽  
Much. Z. Fanani ◽  
Yoko K. Ariga ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Malaria Parasites ◽  
Docking Analysis ◽  
Antimalarial Agent ◽  
Middle Position ◽  
Antimalarial Agents ◽  
Diaphorase Activity

Ferredoxin-NADP+ reductases (FNRs, EC 1.18.1.2) were found in the plastids of Plasmodium and have been considered as a target for the development of new antimalarial agents. Croomine, epi-croomine, tuberostemonine, javastemonine A, and isoprotostemonine are isolated alkaloids from the roots of Stemona sp. and their inhibitory effect on FNRs from Plasmodium falciparum (PfFNR) was investigated. Croomine showed the highest level of inhibition (33.9%) of electron transfer from PfFNR to PfFd, while tuberstemonine displayed the highest level of inhibition (55.4%) of diaphorase activity of PfFNR. Docking analysis represented that croomine is located at the middle position of PfFNR and PfFd. Croomine from S. tuberosa appeared to have potential as an antimalarial agent.

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