A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites

Huber, Werner; Koella, Jacob C.

doi:10.1016/0001-706x(93)90083-n

Cited by 450 publications

(351 citation statements)

References 2 publications

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“…Compounds were measured in duplicate, and results were recorded and expressed as a percentage of the untreated controls. Fifty percent inhibitory concentrations (IC 50 ) were estimated by linear interpolation (56).…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii

Kemp

Rusch²,

Adibekian

et al. 2013

Journal of Biological Chemistry

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Background: S-Palmitoylation is an important reversible modification that involves the action of an acyl-protein thioesterase (APT). Results:We identified an active serine hydrolase (TgASH1) specifically targeted by human APT1 inhibitors in Toxoplasma gondii. Conclusion: TgASH1 is dispensable and cannot be solely responsible for S-depalmitoylation in Apicomplexa. Significance: ␤-Lactone-based APT1 inhibitors hit multiple targets in T. gondii and severely compromise parasite survival.

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Section: Methodsmentioning

confidence: 99%

Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii

Kemp

Rusch²,

Adibekian

et al. 2013

Journal of Biological Chemistry

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“…The activities of miltefosine among the Leishmania species were compared using an analysis of variance and p value ≤ 0.05 was considered to be significant. The IC 50 , IC 90 and CC 50 were calculated using linear regression analysis or interpolation (miniTab 13.0 or microsoft Office Excel 2003) (Huber & Koella 1993). Linear regression was used when the distribution was normal (parametric method) and linear interpolation was applied when the distribution was not normal (non-parametric).…”

Section: Methodsmentioning

confidence: 99%

The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil

Morais-Teixeira

Damasceno

Galuppo

et al. 2011

Mem. Inst. Oswaldo Cruz

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The in vitro leishmanicidal activity of miltefosine® (Zentaris GmbH) was assessed against four medically relevant Leishmania species of Brazil: Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) chagasi. The activity of miltefosine against these New World species was compared to its activity against the Old World strain, Leishmania (Leishmania) donovani, which is known to be sensitive to the effects of miltefosine. The IC50 and IC90 results suggested the New World species harboured similar in vitro susceptibilities to miltefosine; however, miltefosine was approximately 20 times more active against the Old World L. (L.) donovani than against the New World L. (L.) chagasi species. The selectivity index varied from 17.2-28.9 for the New World Leishmania species and up to 420.0 for L. (L.) donovani. The differences in susceptibility to miltefosine suggest that future clinical trials with this drug should include a laboratory pre-evaluation and a dose-defining step

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“…Serial dilutions of inhibitor were prepared in culture medium (0.05-50 M) and added with [ 3 H]hypoxanthine (0.5 Ci/well) to asynchronous cultures at a 0.5% parasitaemia and 2% hematocrit. After a 48-h incubation, the amount of [ 3 H]hypoxanthine incorporated into the parasites was measured, and the concentrations of inhibitor required to prevent incorporation by 50% (EC 50 ) were determined by linear interpolation of inhibition curves (28). Each assay was performed in triplicate on three separate occasions, and data were pooled and are presented as mean Ϯ S.E.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Leucyl Aminopeptidase in Plasmodium falciparum Parasites

Gardiner

Trenholme

Skinner‐Adams

et al. 2006

Journal of Biological Chemistry

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Malaria aminopeptidases are important in the generation and regulation of free amino acids that are used in protein anabolism and for maintaining osmotic stability within the infected erythrocyte. The intraerythrocytic development of malaria parasites is blocked when the activity of aminopeptidases is specifically inhibited by reagents such as bestatin. One of the major aminopeptidases of malaria parasites is a leucyl aminopeptidase of the M17 family. We reasoned that, when this enzyme was the target of bestatin inhibition, its overexpression in malaria cells would lead to a reduced sensitivity to the inhibitor. To address this supposition, transgenic Plasmodium falciparum parasites overexpressing the leucyl aminopeptidase were generated by transfection with a plasmid that housed the full-length gene. Transgenic parasites expressed a 65-kDa protein close to the predicted molecule size of 67.831 kDa for the introduced leucyl aminopeptidase, and immunofluorescence studies localized the protein to the cytosol, the location of the native enzyme. The product of the transgene was shown to be functionally active with cytosolic extracts of transgenic parasites exhibiting twice the leucyl aminopeptidase activity compared with wildtype parasites. In vitro inhibitor sensitivity assays demonstrated that the transgenic parasites were more resistant to bestatin (EC 50 64 M) compared with the parent parasites (EC 50 25 M). Overexpression of genes in malaria parasites would have general application in the identification and validation of targets for antimalarial drugs.

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A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites

Cited by 450 publications

References 2 publications

Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii

Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii

The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil

Overexpression of Leucyl Aminopeptidase in Plasmodium falciparum Parasites

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