Baseline and multinormal distribution of ex vivo susceptibilities of Plasmodium falciparum to methylene blue in Africa, 2013–18

2020 ◽  
Author(s):  
Mathieu Gendrot ◽  
Marylin Madamet ◽  
Joel Mosnier ◽  
Isabelle Fonta ◽  
Rémy Amalvict ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Plasmodium Falciparum ◽  
Ex Vivo ◽  
Geometric Mean ◽  
Threshold Value ◽  
Effective Concentration ◽  
In Vitro Activity ◽  
Potential Partner ◽  
Median Effective Concentration

Abstract Background Plasmodium falciparum resistance to most antimalarial compounds has emerged in Southeast Asia and spread to Africa. In this context, the development of new antimalarial drugs is urgent. Objectives To determine the baseline in vitro activity of methylene blue (Proveblue®) on African isolates and to determine whether parasites have different phenotypes of susceptibility to methylene blue. Methods Ex vivo susceptibility to methylene blue was measured for 609 P. falciparum isolates of patients hospitalized in France for malaria imported from Africa. A Bayesian statistical analysis was designed to describe the distribution of median effective concentration (EC50) estimates. Results The EC50 ranged from 0.16 to 87.2 nM with a geometric mean of 7.17 nM (95% CI = 6.21–8.13). The 609 EC50 values were categorized into four components: A (mean = 2.5 nM; 95% CI = 2.28–2.72), B (mean = 7.44 nM; 95% CI = 7.07–7.81), C (mean = 16.29 nM; 95% CI = 15.40–17.18) and D (mean = 38.49 nM; 95% CI = 34.14–42.84). The threshold value for in vitro reduced susceptibility to methylene blue was estimated at 35 nM using the geometric mean of EC50 plus 2 SDs of the 609 isolates. This cut-off also corresponds to the lower limit of the 95% CI of the methylene blue EC50 of component D. Thirty-five isolates (5.7%) displayed EC50 values above this threshold. Conclusions Methylene blue exerts a promising efficacy against P. falciparum and is a potential partner for triple combinations.

scholarly journals 1-(Ethoxymethyl)-6-(Phenylselenenyl)Pyrimidines with Activity against Human Immunodeficiency Virus Types 1 and 2

1992 ◽  
Vol 3 (5) ◽  
pp. 263-266 ◽  
Author(s):  
N. M. Goudgaon ◽  
A. McMillan ◽  
R. F. Schinazi
Keyword(s):  
Human Lymphocytes ◽  
Fold Increase ◽  
Vero Cells ◽  
Effective Concentration ◽  
In Vitro Activity ◽  
Resistant Virus ◽  
Immunodeficiency Virus ◽  
Median Effective Concentration ◽  
Hiv 1

The reaction of chloromethyl ethyl ether with bis(trimethylsilyl)uracil derivatives yield 1-(ethoxymethyl)pyrimidines 1a–d in good yield. Lithiation of 1a–d with lithium diisopropylamide at −78°C, followed by reaction with diphenyl diselenide as an electrophile, gave 1-(ethoxymethyl)-6-(phenylselenenyl)ura-cils 2a–d in 70–80% yield. The 6-phenylselenenyl acyclic pyrimidines 2b and 2d exhibited selective in vitro activity against HIV-1 and HIV-2 in primary human lymphocytes. The most potent compound was 1-(ethoxymethyl)-6-(phenylselenenyl)-5-ethyluracil 2d with a median effective concentration of 17 nM in primary human lymphocytes and no discernable cytotoxicity in these cells or rapidly dividing CEM and Vero cells. Well characterized AZT-resistant virus was modestly (3 to 12-fold increase) cross-resistant to compounds 2b and 2d.

scholarly journals In Vitro Activity and Interaction of Clindamycin Combined with Dihydroartemisinin against Plasmodium falciparum

2003 ◽  
Vol 47 (11) ◽  
pp. 3494-3499 ◽  
Author(s):  
M. Ramharter ◽  
H. Noedl ◽  
H. Winkler ◽  
W. Graninger ◽  
W. H. Wernsdorfer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Interaction Analysis ◽  
Clinical Investigation ◽  
Effective Concentration ◽  
Significant Activity ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Promising Candidate ◽  
Combination Regimens

ABSTRACT Combination regimens are considered a valuable tool for the fight against drug-resistant falciparum malaria. This study was conducted to evaluate the antimalarial potential of clindamycin in combination with dihydroartemisinin in continuously cultured and in freshly isolated Plasmodium falciparum parasites, measuring the inhibition of Plasmodium falciparum histidine-rich protein II synthesis. Interaction analysis revealed a synergistic or additive mode of interaction at various concentration ratios in all continuously cultured parasites at the 50% effective concentration (EC50) level. Antagonism was not found for any of the culture-adapted parasites. In fresh P. falciparum isolates, a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at the EC50 and EC90 levels. The drug mixture showed no significant activity correlation to other commonly used antimalarials. The clindamycin-dihydroartemisinin combination appears to be a promising candidate for clinical investigation.

scholarly journals In Vitro Activity of Lumefantrine (Benflumetol) against Clinical Isolates of Plasmodium falciparum in Yaoundé, Cameroon

1998 ◽  
Vol 42 (9) ◽  
pp. 2347-2351 ◽  
Author(s):  
Leonardo K. Basco ◽  
Jean Bickii ◽  
Pascal Ringwald
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Geometric Mean ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
In Vitro Activity ◽  
Antimalarial Agents ◽  
Fluorene Derivative

ABSTRACT The in vitro antimalarial activity of the new Chinese synthetic drug, lumefantrine, also known as benflumetol (a fluorene derivative belonging to the aminoalcohol class), was determined by an isotopic microtest against 61 fresh clinical isolates of Plasmodium falciparum and compared with that of other established antimalarial agents. The geometric mean 50% inhibitory concentration of lumefantrine was 11.9 nmol/liter (95% confidence intervals, 10.4 to 13.6 nmol/liter; range, 3.3 to 25.6 nmol/liter). The in vitro activities of lumefantrine against the chloroquine-sensitive and the chloroquine-resistant isolates did not differ (P > 0.05). There was a significant positive correlation of responses between lumefantrine and two other aminoalcohols studied, mefloquine (r = 0.688) and halofantrine (r = 0.677), and between lumefantrine and artesunate (r = 0.420), suggesting a potential for in vitro cross-resistance. Our data suggest high in vitro activity of lumefantrine, comparable to that of mefloquine, and are in agreement with the promising results of preliminary clinical trials.

scholarly journals In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2

2021 ◽  
Vol 10 (14) ◽  
pp. 3007
Author(s):  
Mathieu Gendrot ◽  
Priscilla Jardot ◽  
Océane Delandre ◽  
Manon Boxberger ◽  
Julien Andreani ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Antiviral Activity ◽  
Viral Entry ◽  
Low Cost ◽  
Antiviral Drug ◽  
Effective Concentration ◽  
Rt Pcr ◽  
Post Entry ◽  
Median Effective Concentration

A new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19), which emerged in Wuhan, China in December 2019, has spread worldwide. Currently, very few treatments are officially recommended against SARS-CoV-2. Identifying effective, low-cost antiviral drugs with limited side effects that are affordable immediately is urgently needed. Methylene blue, a synthesized thiazine dye, may be a potential antiviral drug. Antiviral activity of methylene blue used alone or in combination with several antimalarial drugs or remdesivir was assessed against infected Vero E6 cells infected with two clinically isolated SARS-CoV-2 strains (IHUMI-3 and IHUMI-6). Effects both on viral entry in the cell and on post-entry were also investigated. After 48 h post-infection, the viral replication was estimated by RT-PCR. The median effective concentration (EC50) and 90% effective concentration (EC90) of methylene blue against IHUMI-3 were 0.41 ± 0.34 µM and 1.85 ± 1.41 µM, respectively; 1.06 ± 0.46 µM and 5.68 ± 1.83 µM against IHUMI-6. Methylene blue interacted at both entry and post-entry stages of SARS-CoV-2 infection in Vero E6 cells as retrieved for hydroxychloroquine. The effects of methylene blue were additive with those of quinine, mefloquine and pyronaridine. The combinations of methylene blue with chloroquine, hydroxychloroquine, desethylamodiaquine, piperaquine, lumefantrine, ferroquine, dihydroartemisinin and remdesivir were antagonist. These results support the potential interest of methylene blue to treat COVID-19.

scholarly journals PotentEx VivoActivity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

2015 ◽  
Vol 59 (10) ◽  
pp. 6117-6124 ◽  
Author(s):  
Grennady Wirjanata ◽  
Boni F. Sebayang ◽  
Ferryanto Chalfein ◽  
Prayoga ◽  
Irene Handayuni ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Plasmodium Falciparum ◽  
Ex Vivo ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Trophozoite Stage ◽  
Content Type ◽  
Susceptibility Data ◽  
Highly Active

ABSTRACTThe 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potentin vitroefficacies againstPlasmodium falciparum, but susceptibility data forP. vivaxare limited. The species- and stage-specificex vivoactivities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistantP. falciparumandP. vivaxare prevalent. Both compounds were highly active againstP. falciparum(median [range] 50% inhibitory concentration [IC50]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) andP. vivax(NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC50s in parasites exposed at the trophozoite stage than at the ring stage for NQ inP. falciparum(26.5 versus 5.1 nM,P= 0.021) andP. vivax(341.6 versus 6.5 nM,P= 0.021) and for MB inP. vivax(10.1 versus 1.6 nM,P= 0.010). The excellentex vivoactivities of NQ and MB against bothP. falciparumandP. vivaxhighlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.

scholarly journals In Vitro Activity of Tafenoquine against the Asexual Blood Stages of Plasmodium falciparum Isolates from Gabon, Senegal, and Djibouti

2006 ◽  
Vol 50 (9) ◽  
pp. 3225-3226 ◽  
Author(s):  
Bruno Pradines ◽  
Modeste Mabika Mamfoumbi ◽  
Adama Tall ◽  
Cheikh Sokhna ◽  
Jean-Louis Koeck ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vitro Activity ◽  
In Vitro Activity

scholarly journals Synthesis of New 4-Aminoquinolines and Evaluation of Their In Vitro Activity against Chloroquine-Sensitive and Chloroquine-Resistant Plasmodium falciparum

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140878 ◽  
Author(s):  
Chandima S. K. Rajapakse ◽  
Maryna Lisai ◽  
Christiane Deregnaucourt ◽  
Véronique Sinou ◽  
Christine Latour ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vitro Activity ◽  
In Vitro Activity
Sign in / Sign up

Export Citation Format

Share Document