scholarly journals In Vitro Activities of Benflumetol against 158 Senegalese Isolates of Plasmodium falciparum in Comparison with Those of Standard Antimalarial Drugs

1999 ◽  
Vol 43 (2) ◽  
pp. 418-420 ◽  
Author(s):  
Bruno Pradines ◽  
Adama Tall ◽  
Thierry Fusai ◽  
Andre Spiegel ◽  
Remi Hienne ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Antimalarial Drugs ◽  
Cross Resistance ◽  
Alternative Drug

ABSTRACT The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%) showed decreased susceptibility to benflumetol. Benflumetol was slightly more potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak correlations in the responses to benflumetol and pyrimethamine, chloroquine, amodiaquine, artemether, quinine, and pyronaridine were observed, and these correlations are insufficient to suggest cross-resistance. Benflumetol may be an important alternative drug for the treatment of chloroquine-resistant malaria.

In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine

Parasitology ◽  
1998 ◽  
Vol 117 (6) ◽  
pp. 541-545 ◽  
Author(s):  
B. PRADINES ◽  
M. MABIKA MAMFOUMBI ◽  
D. PARZY ◽  
M. OWONO MEDANG ◽  
C. LEBEAU ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Narrow Range ◽  
Drug Susceptibility ◽  
Drug Uptake ◽  
Cross Resistance ◽  
In Vitro Susceptibility ◽  
Positive Correlation ◽  
Common Features

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0·8 to 34·8 nm (mean IC50 5·0 nm) and the 95% confidence interval (CI95%) was 3·6–6·3 nm. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2=0·45, P<0·001), artemether and chloroquine (r2=0·36, P<0·001), artemether and quinine (r2=0·31, P<0·001), and artemether and halofantrine r2=0·19, P<0·01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.

scholarly journals Hybrid Gold(I) NHC-Artemether Complexes to Target Falciparum Malaria Parasites

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2817
Author(s):  
Manel Ouji ◽  
Guillaume Barnoin ◽  
Álvaro Fernández Álvarez ◽  
Jean-Michel Augereau ◽  
Catherine Hemmert ◽  
...  
Keyword(s):  
Public Health ◽  
Plasmodium Falciparum ◽  
Mammalian Cells ◽  
Antimalarial Drugs ◽  
Cross Resistance ◽  
Major Threat ◽  
Hybrid Molecules ◽  
Low Cytotoxicity ◽  
Nanomolar Range

The emergence of Plasmodium falciparum parasites, responsible for malaria disease, resistant to antiplasmodial drugs including the artemisinins, represents a major threat to public health. Therefore, the development of new antimalarial drugs or combinations is urgently required. In this context, several hybrid molecules combining a dihydroartemisinin derivative and gold(I) N-heterocyclic carbene (NHC) complexes have been synthesized based on the different modes of action of the two compounds. The antiplasmodial activity of these molecules was assessed in vitro as well as their cytotoxicity against mammalian cells. All the hybrid molecules tested showed efficacy against P. falciparum, in a nanomolar range for the most active, associated with a low cytotoxicity. However, cross-resistance between artemisinin and these hybrid molecules was evidenced. These results underline a fear about the risk of cross-resistance between artemisinins and new antimalarial drugs based on an endoperoxide part. This study thus raises concerns about the use of such molecules in future therapeutic malaria policies.

scholarly journals Statins as Potential Antimalarial Drugs: Low Relative Potency and Lack of Synergy with Conventional Antimalarial Drugs

2009 ◽  
Vol 53 (5) ◽  
pp. 2212-2214 ◽  
Author(s):  
Rina P. M. Wong ◽  
Timothy M. E. Davis
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Antimalarial Drugs ◽  
Relative Potency ◽  
Treated Subject ◽  
In Vitro Sensitivity ◽  
Weak Activity ◽  
Resistant Strains

ABSTRACT The in vitro sensitivity of Plasmodium falciparum to atorvastatin and rosuvastatin was assessed using chloroquine-sensitive and chloroquine-resistant strains. Although atorvastatin was more potent, it had weak activity (mean 50% inhibitory concentration of ≥17 μM) and an indifferent interaction with chloroquine and dihydroartemisinin. Bioassay of plasma from an atorvastatin-treated subject showed similar results.

scholarly journals Atorvastatin Is a Promising Partner for Antimalarial Drugs in Treatment of Plasmodium falciparum Malaria

2009 ◽  
Vol 53 (6) ◽  
pp. 2248-2252 ◽  
Author(s):  
Véronique Parquet ◽  
Sébastien Briolant ◽  
Marylin Torrentino-Madamet ◽  
Maud Henry ◽  
Lionel Almeras ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Reductase Inhibitor ◽  
Significant Positive Correlation ◽  
Plasmodium Falciparum Malaria ◽  
Antimalarial Drugs ◽  
Transport Proteins ◽  
Cross Resistance ◽  
Antimalarial Drug Resistance

ABSTRACT Atorvastatin (AVA) is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. AVA exposure resulted in the reduced in vitro growth of 22 Plasmodium falciparum strains, with the 50% inhibitory concentrations (IC50s) ranging from 2.5 μM to 10.8 μM. A significant positive correlation was found between the strains’ responses to AVA and mefloquine (r = 0.553; P = 0.008). We found no correlation between the responses to AVA and to chloroquine, quinine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone, or doxycycline. These data could suggest that the mechanism of AVA uptake and/or the mode of action of AVA is different from those for other antimalarial drugs. The IC50s for AVA were unrelated to the occurrence of mutations in the transport protein genes involved in quinoline antimalarial drug resistance, such as the P. falciparum crt, mdr1, mrp, and nhe-1 genes. Therefore, AVA can be ruled out as a substrate for the transport proteins (CRT, Pgh1, and MRP) and is not subject to the pH modification induced by the P. falciparum NHE-1 protein. The absence of in vitro cross-resistance between AVA and chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone, and doxycycline argues that these antimalarial drugs could potentially be paired with AVA as a treatment for malaria. In conclusion, the present observations suggest that AVA is a good candidate for further studies on the use of statins in association with drugs known to have activities against the malaria parasite.

scholarly journals Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in African Plasmodium falciparum

2021 ◽  
Vol 14 (4) ◽  
pp. 351
Author(s):  
Mathieu Gendrot ◽  
Océane Delandre ◽  
Marie Robert ◽  
Francis Foguim ◽  
Nicolas Benoit ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Cross Resistance ◽  
Antimalarial Drug Resistance ◽  
In Vitro Susceptibility

Half the human population is exposed to malaria. Plasmodium falciparum antimalarial drug resistance monitoring and development of new drugs are major issues related to the control of malaria. Methylene blue (MB), the oldest synthetic antimalarial, is again a promising drug after the break of its use as an antimalarial drug for more than 80 years and a potential partner for triple combination. Very few data are available on the involvement of polymorphisms on genes known to be associated with standard antimalarial drugs and parasite in vitro susceptibility to MB (cross-resistance). In this context, MB susceptibility was evaluated against 482 isolates of imported malaria from Africa by HRP2-based ELISA chemosusceptibility assay. A total of 12 genes involved in antimalarial drug resistance (Pfcrt, Pfdhfr, Pfmdr1, Pfmdr5, Pfmdr6, PfK13, Pfubq, Pfcarl, Pfugt, Pfact, Pfcoronin, and copy number of Pfpm2) were sequenced by Sanger method and quantitative PCR. On the Pfmdr1 gene, the mutation 86Y combined with 184F led to more susceptible isolates to MB (8.0 nM vs. 11.6 nM, p = 0.03). Concerning Pfmdr6, the isolates bearing 12 Asn repetitions were more susceptible to MB (4.6 nM vs. 11.6 nM, p = 0.005). None of the polymorphisms previously described as involved in antimalarial drug resistance was shown to be associated with reduced susceptibility to MB. Some genes (particularly PfK13, Pfugt, Pfact, Pfpm2) did not present enough genetic variability to draw conclusions about their involvement in reduced susceptibility to MB. None of the polymorphisms analyzed by multiple correspondence analysis (MCA) had an impact on the MB susceptibility of the samples successfully included in the analysis. It seems that there is no in vitro cross-resistance between MB and commonly used antimalarial drugs.

scholarly journals Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory Concentration

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

ABSTRACT The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

Drug sensitivity of Plasmodium falciparum field isolates to selected antimalarial drugs in Ghana using the in-vitro DAPI assay

2020 ◽  
Author(s):  
Michael Fokuo Ofori ◽  
Emma E. Kploanyi ◽  
Benedicta A. Mensah ◽  
Emmanuel K. Dickson ◽  
Eric Kyei Baafour ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Sensitivity ◽  
Geometric Mean ◽  
Antimalarial Drugs ◽  
Chloroquine Resistance ◽  
Cape Coast ◽  
African Region ◽  
Cross Sectional ◽  
Ecological Zones

Abstract Background: Malaria continues to be a major health issue globally with nine out of ten cases reported in Africa. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum parasite, compounding evidence of artemisinin and amodiaquine resistance in the African region establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies.Methods: The study was cross-sectional and was conducted during the peak transmission seasons of 2015, 2016, and 2017 in two study sites located in different ecological zones of Ghana involving children aged 0.5-14 years presenting with symptomatic uncomplicated Plasmodium falciparum (Pf) malaria with parasitaemia greater than 1000 parasites/µl of blood. Using in vitro 4-,6-diamidino-2-phenylindole (DAPI) drug sensitivity assays, 328 Pf parasites collected were used to investigate susceptibility to five selected antimalarial drugs: chloroquine, amodiaquine, dihydroartemisinin, artesunate and mefloquine.Results: The geometric mean B (GMIC50) of five drugs against the parasites collected from Cape Coast were 9.6, 23.6, 9.1, 3.5 and 8.1nM for chloroquine, amodiaquine, artemisinin, artesunate, and mefloquine respectively in 2015. There was a 2 fold increase in the GMIC50 levels of all the drugs against the isolates collected in 2016 as compared to the 2015 data from Cape Coast .The a of the five drugs against the parasites collected from Cape Coast were significantly higher than those isolates collected from Begoro in 2016 and 2017 (P<0.001) . The chloroquine resistance ranged between 1.9% and 9.1% among isolates collected from Cape Coast but remained 0% in Begoro over the period. High amodiaquine resistance levels were recorded at both sites whilst that of artesunate resistance ranged between 4 and 10% over the study period.Conclusions: The study has assessed the antimalarial drug sensitivities of Ghanaian Pf isolates collected over 3 consecutive years. The parasites showed variable resistance levels to all the drugs used over the period. The study has demonstrated the continual return of chloroquine-sensitive parasites. The in vitro DAPI assay is a useful method for monitoring individual drugs used in combinations in Ghana for the generation of data on their sensitivities over time.

scholarly journals IN VITRO POTENCY AND TOXICITY OF STREPTOMYCES SP. FERMENTATION PRODUCT AS AN ANTIMALARIAL THERAPY AGAINST PLASMODIUM FALCIPARUM

2019 ◽  
pp. 251-255
Author(s):  
YUNI SETYANINGSIH ◽  
ABDUL LATIF ◽  
HENDRI ASTUTY ◽  
DIN SYAFRUDDIN ◽  
PUJI BUDI SETIA ASIH
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Toxicity Tests ◽  
Streptomyces Sp ◽  
No Formation ◽  
Fermentation Product ◽  
Transmission Electron ◽  
In Vitro Technique ◽  
Antimalarial Therapy

Objective: This research aims to study the activity of a Streptomyces sp. fermentation product as an antimalarial modality in HepG2 cells.Methods: The effects of the product against Plasmodium falciparum 3D7 were examined using an in vitro technique parasite. The potency of theStreptomyces sp. fermentation product was examined by determining the half maximal inhibitory concentration (IC50), and the mechanism wasstudied using transmission electron microscopy (TEM). Toxicity tests were also conducted.Results: The Streptomyces sp. fermentation product had an IC50 of 0.001 μg/ml against the parasite, versus values of 0.054 and 0.022 μg/ml forquinidine and prodigiosin, respectively. TEM revealed no formation of hemozoin. The Streptomyces sp. fermentation product was non-toxic in HepG2cells based on its cytotoxicity concentration 50% of 1.380 μg/ml.Conclusion: The Streptomyces sp. fermentation product has potential as a potent and non-toxic antimalarial therapy.

scholarly journals In Vitro Assessment of Antiplasmodial Activity and Cytotoxicity of Polyalthia longifolia Leaf Extracts on Plasmodium falciparum Strain NF54

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Bethel Kwansa-Bentum ◽  
Kojo Agyeman ◽  
Jeffrey Larbi-Akor ◽  
Claudia Anyigba ◽  
Regina Appiah-Opong
Keyword(s):  
Plasmodium Falciparum ◽  
Ethyl Acetate ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Radical Scavenging ◽  
Antimalarial Drugs ◽  
Antiplasmodial Activity ◽  
Leaf Extracts ◽  
Polyalthia Longifolia

Background. Malaria is one of the most important life-threatening infectious diseases in the tropics. In spite of the effectiveness of artemisinin-based combination therapy, reports on reduced sensitivity of the parasite to artemisinin in Cambodia and Thailand warrants screening for new potential antimalarial drugs for future use. Ghanaian herbalists claim that Polyalthia longifolia has antimalarial activity. Therefore, antiplasmodial activity, cytotoxic effects, and antioxidant and phytochemical properties of P. longifolia leaf extract were investigated in this study. Methodology/Principal Findings. Aqueous, 70% hydroethanolic and ethyl acetate leaf extracts were prepared using standard procedures. Antiplasmodial activity was assessed in vitro by using chloroquine-sensitive malaria parasite strain NF54. The SYBR® Green and tetrazolium-based calorimetric assays were used to measure parasite growth inhibition and cytotoxicity, respectively, after extract treatment. Total antioxidant activity was evaluated using a free radical scavenging assay. Results obtained showed that extracts protected red blood cells against Plasmodium falciparum mediated damage. Fifty percent inhibitory concentration (IC50) values were 24.0±1.08 μg/ml, 22.5±0.12 μg/ml, and 9.5±0.69 μg/ml for aqueous, hydroethanolic, and ethyl acetate extracts, respectively. Flavonoids, tannins, and saponins were present in the hydroethanolic extract, whereas only the latter was observed in the aqueous extract. Aqueous and hydroethanolic extracts showed stronger antioxidant activities compared to the ethyl acetate extract. Conclusions/Significance. The extracts of P. longifolia have antiplasmodial properties and low toxicities to human red blood cells. The extracts could be developed as useful alternatives to antimalarial drugs. These results support claims of the herbalists that decoctions of P. longifolia are useful antimalarial agents.

The in vitro antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with mefloquine/artesunate

2014 ◽  
Vol 60 (1) ◽  
Author(s):  
Wanna Chaijaroenkul ◽  
Kesara Na-Bangchang
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Drug Concentration ◽  
Combination Index ◽  
Antimalarial Drugs ◽  
Antagonistic Effect ◽  
Parasite Growth ◽  
Major Health Problem ◽  
Major Health

AbstractMultidrug resistance Plasmodium falciparum is the major health problem in Thailand. Discovery and development of new antimalarial drugs with novel modes of action is urgently required. The aim of the present study was to investigate the antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with the standard antimalarial drugs mefloquine and artesunate in chloroquine sensitive (3D7) and chloroquine resistant (K1) P. falciparum clones in vitro. Median (range) IC50 (drug concentration which produces 50% parasite growth inhibition) values of the 9-hydroxycalabaxanthone, α-mangostin, artesunate and mefloquine for 3D7 vs K1 clones were 1.5 (0.9-2.1) vs 1.2 (1.1-1.6) μM, 17.9 (15.7.0-20.0) vs 9.7 (6.0-14.0) μM, 1.0 (0.4-3.0) vs 1.7 (1.0-2.5) nM, and 13.3 (11.1-13.3) vs 7.1 (6.7-12.2) nM, respectively. Analysis of isobologram and combination index (CI) of 9-hydroxycalabaxanthone with artesunate or mefloquine showed synergistic and indifference antimalarial interaction, respectively. α-mangostin-artesunate combination exhibited a slight antagonistic effect of antimalarial interaction, whereas α-mangostin and mefloquine combination showed indifference interaction in both clones. The combination of 9-hydroxycalabaxanthone with α-mangostin showed the synergistic antimalarial interaction in both clones

Sign in / Sign up

Export Citation Format

Share Document