scholarly journals In Vitro Activities of DU-1102, a New Trioxaquine Derivative, against Plasmodium falciparum Isolates

2001 ◽  
Vol 45 (6) ◽  
pp. 1886-1888 ◽  
Author(s):  
Leonardo K. Basco ◽  
Odile Dechy-Cabaret ◽  
Mathieu Ndounga ◽  
Fleurette Solange Meche ◽  
Anne Robert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mode Of Action ◽  
Inhibitory Concentration ◽  
Covalent Linkage ◽  
Highly Active ◽  
Low Correlation ◽  
Independent Mode

ABSTRACT The antimalarial trioxaquine derivative DU-1102, synthesized by covalent linkage between aminoquinoline and trioxane moieties, was highly active against Cameroonian isolates (mean 50% inhibitory concentration of 43 nmol/liter) of Plasmodium falciparum. There was no correlation between the responses to DU-1102 and chloroquine and only a low correlation between the responses to DU-1102 and pyrimethamine, suggesting an independent mode of action of the trioxaquine against the parasites.

scholarly journals In Vitro Activities of Piperaquine and Other 4-Aminoquinolines against Clinical Isolates of Plasmodium falciparum in Cameroon

2003 ◽  
Vol 47 (4) ◽  
pp. 1391-1394 ◽  
Author(s):  
Leonardo K. Basco ◽  
Pascal Ringwald
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Central Africa ◽  
New Drugs ◽  
Clinical Isolates ◽  
Highly Active ◽  
Synthetic Drug ◽  
Further Development

ABSTRACT The spread of chloroquine-resistant Plasmodium falciparum calls for a constant search for new drugs. The in vitro activity of piperaquine, a new Chinese synthetic drug belonging to the bisquinolines, was evaluated in 103 fresh clinical isolates of P. falciparum in Cameroon, Central Africa, and compared with that of other 4-aminoquinoline and Mannich base derivatives and dihydroartemisinin. Piperaquine was highly active (geometric mean 50% inhibitory concentration, 38.9 nmol/liter; range, 7.76 to 78.3 nmol/liter) and equally active (P > 0.05) against the chloroquine-sensitive and the chloroquine-resistant isolates. There was a significant but low correlation of response between chloroquine and piperaquine (r = 0.257, P < 0.05). These results suggest that further development of piperaquine, in combination with dihydroartemisinin, holds promise for use in chloroquine-resistant regions of endemicity.

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.

scholarly journals Effect of Fluorescent Dyes onIn Vitro-Differentiated, Late-Stage Plasmodium falciparum Gametocytes

2014 ◽  
Vol 58 (12) ◽  
pp. 7398-7404 ◽  
Author(s):  
Tamirat Gebru ◽  
Benjamin Mordmüller ◽  
Jana Held
Keyword(s):  
Plasmodium Falciparum ◽  
Late Stage ◽  
Fluorescent Dyes ◽  
Clinical Symptoms ◽  
Laboratory Strain ◽  
Clinical Isolates ◽  
Synthetic Dyes ◽  
Content Type ◽  
Highly Active

ABSTRACTPlasmodium falciparumgametocytes are not associated with clinical symptoms, but they are responsible for transmitting the pathogen to mosquitoes. Therefore, gametocytocidal interventions are important for malaria control and resistance containment. Currently available drugs and vaccines are not well suited for that purpose. Several dyes have potent antimicrobial activity, but their use against gametocytes has not been investigated systematically. The gametocytocidal activity of nine synthetic dyes and four control compounds was tested against stage V gametocytes of the laboratory strain 3D7 and three clinical isolates ofP. falciparumwith a bioluminescence assay. Five of the fluorescent dyes had submicromolar 50% inhibitory concentration (IC50) values against mature gametocytes. Three mitochondrial dyes, MitoRed, dihexyloxacarbocyanine iodide (DiOC6), and rhodamine B, were highly active (IC50s < 200 nM). MitoRed showed the highest activity against gametocytes, with IC50s of 70 nM against 3D7 and 120 to 210 nM against clinical isolates. All compounds were more active against the laboratory strain 3D7 than against clinical isolates. In particular, the endoperoxides artesunate and dihydroartemisinin showed a 10-fold higher activity against 3D7 than against clinical isolates. In contrast to all clinically used antimalarials, several fluorescent dyes had surprisingly highin vitroactivity against late-stage gametocytes. Since they also act against asexual blood stages, they shall be considered starting points for the development of new antimalarial lead compounds.

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 The Effect of Aqueous Extract of Cinnamon on the Metabolome ofPlasmodium falciparumUsing1HNMR Spectroscopy

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Shirin Parvazi ◽  
Sedigheh Sadeghi ◽  
Mehri Azadi ◽  
Maryam Mohammadi ◽  
Mohammad Arjmand ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Aqueous Extract ◽  
Drug Targets ◽  
Inhibitory Concentration ◽  
Biological Fluids ◽  
Medicinal Herbs ◽  
New Drugs ◽  
Lysine Biosynthesis ◽  
Glutathione Metabolism

Malaria is responsible for estimated 584,000 deaths in 2013. Researchers are working on new drugs and medicinal herbs due to drug resistance that is a major problem facing them; the search is on for new medicinal herbs. Cinnamon is the bark of a tree with reported antiparasitic effects. Metabonomics is the simultaneous study of all the metabolites in biological fluids, cells, and tissues detected by high throughput technology. It was decided to determine the mechanism of the effect of aqueous extract of cinnamon on the metabolome ofPlasmodium falciparum in vitrousing1HNMR spectroscopy. Prepared aqueous extract of cinnamon was added to a culture ofPlasmodium falciparum3D7 and its 50% inhibitory concentration determined, and, after collection, their metabolites were extracted and1HNMR spectroscopy by NOESY method was done. The spectra were analyzed by chemometric methods. The differentiating metabolites were identified using Human Metabolome Database and the metabolic cycles identified by Metaboanalyst. 50% inhibitory concentration of cinnamon onPlasmodium falciparumwas 1.25 mg/mL withp<0.001. The metabolites were identified as succinic acid, glutathione, L-aspartic acid, beta-alanine, and 2-methylbutyryl glycine. The main metabolic cycles detected were alanine and aspartame and glutamate pathway and pantothenate and coenzyme A biosynthesis and lysine biosynthesis and glutathione metabolism, which are all important as drug targets.

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 Plasmodium falciparum: In Vitro Cytotoxicity Testing Using MTT

1998 ◽  
Vol 3 (1) ◽  
pp. 49-53 ◽  
Author(s):  
J. Enrico Lazaro ◽  
Frederick Gay
Keyword(s):  
Plasmodium Falciparum ◽  
Culture System ◽  
Inhibitory Concentration ◽  
In Vitro Cytotoxicity ◽  
Mtt Method ◽  
Diphenyltetrazolium Bromide ◽  
Wide Range ◽  
In Vitro Culture System ◽  
Comparative Results

The microculture tetrazolium assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was used to estimate the 50% inhibitory concentration of chloroquine, quinine, artemisinin, and atovaquone using a Plasmodium falciparum in vitro culture system. The MTT assay was compared to the standard tritiated hypoxan-thine assay and to a previously described method, the 2,2′-di-p-nitrophenyl-5,5′-diphenyl-3,3′-[3,3′-dimethoxy-4,4′-diphenylenel-ditetrazolium chloride (NBT) assay. In general, the results show that the three assays generate comparative results. The results of this study suggest that the MTT method is able to give a profile of cytotoxic dose response effects over a wide range of concentrations of a drug. The method may be used in work that does not require extreme pre-cision and sensitivity, for instance, as a portable rapid screen to assay natural products for in vitro cytotoxic ac-tivity against Plasmodium falciparum.

In Vitro Activities of StrychnosAlkaloids and Extracts against Plasmodium falciparum

1999 ◽  
Vol 43 (9) ◽  
pp. 2328-2331 ◽  
Author(s):  
Michel Frederich ◽  
Marie-Pierre Hayette ◽  
Monique Tits ◽  
Patrick De Mol ◽  
Luc Angenot
Keyword(s):  
Plasmodium Falciparum ◽  
Resistant Strain ◽  
Inhibitory Concentration ◽  
Sensitive Strain ◽  
Resistant Strains

ABSTRACT The in vitro antimalarial activities of 46 alkaloids and extracts from Strychnos species were evaluated. Two types of quasidimeric alkaloids exhibit high and selective activities againstPlasmodium. Strychnopentamine and isostrychnopentamine were active against chloroquine-sensitive and -resistant strains (50% inhibitory concentration [IC50] ≈ 0.15 μM), while dihydrousambarensine exhibited a 30-fold higher activity against the chloroquine-resistant strain (IC50 = 0.03 μM) than it did against the chloroquine-sensitive strain.

scholarly journals A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4485
Author(s):  
Veronika R. Karpina ◽  
Svitlana S. Kovalenko ◽  
Sergiy M. Kovalenko ◽  
Oleksandr G. Drushlyak ◽  
Natalya D. Bunyatyan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Inhibitory Concentration ◽  
Antimalarial Activity ◽  
Virtual Library ◽  
Antimalarial Agents ◽  
Starting Point ◽  
In Silico Studies

For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC50 = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.

scholarly journals In Vitro Sensitivities of Plasmodium falciparum to Different Antimalarial Drugs in Uganda

2010 ◽  
Vol 54 (3) ◽  
pp. 1200-1206 ◽  
Author(s):  
Samuel L. Nsobya ◽  
Moses Kiggundu ◽  
Sarah Nanyunja ◽  
Moses Joloba ◽  
Bryan Greenhouse ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Drug Efficacy ◽  
New Combination ◽  
Efficacy Trial ◽  
Wide Range ◽  
Highly Correlated ◽  
Multiple Drugs ◽  
Combination Regimens

ABSTRACT The control of malaria is challenged by resistance of Plasmodium falciparum to multiple drugs. New combination regimens are now advocated for the treatment of uncomplicated falciparum malaria, but the extent of resistance to newer agents is incompletely understood. We measured the in vitro sensitivity of P. falciparum parasites cultured from children enrolled in a drug efficacy trial in Kampala, Uganda, from 2006 to 2008. Sensitivities were measured by comparing levels of histidine-rich protein-2 in parasites incubated with different concentrations of drugs with those in untreated controls. The cultured parasites exhibited a wide range of sensitivities to chloroquine (CQ); monodesethylamodiaquine (MDAQ), the major active metabolite of amodiaquine; and quinine (QN). Mean 50% inhibitory concentration (IC50) results were above standard cutoffs for resistance for CQ and MDAQ. Parasites were generally sensitive to dihydroartemisinin (DHA), lumefantrine (LM), and piperaquine (PQ). For CQ, MDAQ, and QN but not the other drugs, activities against individual strains were highly correlated. We also assessed known resistance-mediating polymorphisms in two putative transporters, pfcrt and pfmdr1. When parasites that were least and most sensitive to each drug were compared, the pfmdr1 86Y mutation was significantly more common in parasites that were most resistant to CQ and MDAQ, and the pfmdr1 D1246Y mutation was significantly more common in parasites that were most resistant to MDAQ and QN. In summary, we demonstrated in parasites from Kampala a range of sensitivities to older drugs; correlation of sensitivities to CQ, MDAQ, and QN; and good activity against nearly all strains for DHA, LM, and PQ.

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