In vitro assays to determine drug sensitivities of African trypanosomes: a review

Kaminsky, Ronald; Brun, Reto

doi:10.1016/0001-706x(93)90100-p

Cited by 33 publications

(14 citation statements)

References 32 publications

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“…Compounds were initially tested at 10 nM, 100 nM or 1 μM, to define a range where cell density responded to drug concentrations. Then, at least five drug concentrations26 covering this range was used for subsequent assays. Each concentration was tested in duplicate.…”

Section: Methodsmentioning

confidence: 99%

Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis

Thomas

Purmal

Pollastri

et al. 2016

Sci Rep

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The protozoan parasite Trypanosoma brucei causes the fatal illness human African trypanosomiasis (HAT). Standard of care medications currently used to treat HAT have severe limitations, and there is a need to find new chemical entities that are active against infections of T. brucei. Following a “drug repurposing” approach, we tested anti-trypanosomal effects of carbazole-derived compounds called “Curaxins”. In vitro screening of 26 compounds revealed 22 with nanomolar potency against axenically cultured bloodstream trypanosomes. In a murine model of HAT, oral administration of compound 1 cured the disease. These studies established 1 as a lead for development of drugs against HAT. Pharmacological time-course studies revealed the primary effect of 1 to be concurrent inhibition of mitosis coupled with aberrant licensing of S-phase entry. Consequently, polyploid trypanosomes containing 8C equivalent of DNA per nucleus and three or four kinetoplasts were produced. These effects of 1 on the trypanosome are reminiscent of “mitotic slippage” or endoreplication observed in some other eukaryotes.

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Section: Methodsmentioning

confidence: 99%

Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis

Thomas

Purmal

Pollastri

et al. 2016

Sci Rep

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“…As far as we know, there is no previous study on the comparison of in vitro trypanocidal activities between different pharmaceutical formulations and their corresponding active principles. Although MIC determination was considered for many years as a reliable technique, these results must be confirmed using a more accurate technique such as 3H-hypoxanthine incorporation assay (Kaminsky and Brun, 1993). These preliminary results suggest that standardization of in vitro assay protocols is required and should be based on the use of active principles to ensure drug quality and purity that permits rationale and therefore to allow comparison of MIC between laboratories.…”

Section: Resultsmentioning

confidence: 98%

“…The long-term viability assay was used to determine the MIC for both the active principle and the corresponding commercial formulation in the same 24-well plates (Kaminsky and Brun, 1993). The trypanosomes (10 5 parasites/ml) were exposed for 10 days to twofold serial drug dilutions ranging from 0.462 to 7.39 µg/ml DFMO and 0.5 to 8 µg/ml Ornidyl®, 0.2 to 3.2 µg/ml for both suramine sodium salt and Germanin®, 0.0005 to 0.008 µg/ml for both Pentamidine isethionate® and pentamidine isethionate sodium salt, and 0.625 to 10 µg/ml for both Lampit® and 5-nitrofuran.…”

Section: Methodsmentioning

confidence: 99%

“…Cases of treatment failure have been reported in Central Africa (Ollivier and Legros, 2001), and drugresistant parasites are spreading. For example, in Angola (Kaminsky and Brun, 1993). The active principle is a pure compound, and its use is probably more reliable than commercial formulations, especially for long-term or multicentric in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro activity of commercial formulation and active principle of trypanocidal drugs against blooststreams forms of Trypanosoma brucei gambiense

Likeufack¹,

Tongue²,

Truc³

2003

Afr. J. Biotechnol.

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The in vitro trypanocidal activities of 4 commercial formulations Ornidyl®, Pentamidine isethionate®, Germanin® and Lampit® and their corresponding active principles (Dl-α-difluoromethylornithine, pentamidine isethionate, suramine and 5-nitrofuran) were compared against Trypanosoma brucei gambiense. Differences of minimum inhibitory concentration (MIC) were observed between Ornidyl® and Dl-α-difluoromethylornithine and between Lampit® and 5-nitrofuran. For RO 15 strain and the comparison of Ornidyl®/ DFMO, the MIC when using the commercial drug was more than twice the MIC value obtained with the active principle. For all 3 trypanosome strains, MICs were identical for Lampit® and 5-nitrofuran but the MIC with the commercial formulation was twice the MIC obtained with the active principle. The active principles, rather than commercial formulations, should be used for standardization of in vitro assay protocols.

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“…Parasites motility constitute a relatively reliable indicator of viability of most zoo flagellate parasites and an arrest or drop in motility of trypanosomes may serve as a measure of anti-trypanosomal activity of plant extracts when compared to the control, phosphate-glucose buffer saline [23] . Similarly, it has been reported that a complete elimination or reduction of motility of parasites when compared to the control could be taken as index of trypanocidal activity [21] .…”

Section: Discussionmentioning

confidence: 99%