The establishment of in vitro culture and drug screening systems for a newly isolated strain of Trypanosoma equiperdum

Suganuma, Keisuke; Yamasaki, Shino; Molefe, Nthatisi Innocentia; Musinguzi, Peter; Davaasuren, Batdorj; Mossaad, Ehab; Narantsatsral, Sandagdorj; Battur, Banzragch; Battsetseg, Badgar; Inoue, Noboru

doi:10.1016/j.ijpddr.2017.04.002

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…The trypanocidal activity and cytotoxicity of nitrofurantoin analogs were evaluated according to previous reports [ 34 , 35 ], with some modifications. In brief, bloodstream forms adjusted at 2.5 × 10 3 cells/mL ( T. b. brucei GUTat3.1, T. b. gambiense IL1922, and T. b. rhodesiense IL1501), 1 × 10 4 cells/mL ( T. evansi Tansui and T. b. rhodesiense Chirundu), and 1 × 10 5 cells/mL ( T. congolense IL3000), were cultivated in Nunc ® MicroWell 96-well optical bottom plates (Thermo Fisher Scientific, Waltham, MA, USA) and exposed to various analogs at seven different concentrations for 3 days, in an incubator at 37 °C (33 °C for T. congolense IL3000).…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

et al. 2021

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African trypanosomes cause diseases in humans and livestock. Human African trypanosomiasis is caused by Trypanosoma brucei rhodesiense and T. b. gambiense. Animal trypanosomoses have major effects on livestock production and the economy in developing countries, with disease management depending mainly on chemotherapy. Moreover, only few drugs are available and these have adverse effects on patients, are costly, show poor accessibility, and parasites develop drug resistance to them. Therefore, novel trypanocidal drugs are urgently needed. Here, the effects of synthesized nitrofurantoin analogs were evaluated against six species/strains of animal and human trypanosomes, and the treatment efficacy of the selected compounds was assessed in vivo. Analogs 11 and 12, containing 11- and 12-carbon aliphatic chains, respectively, showed the highest trypanocidal activity (IC50 < 0.34 µM) and the lowest cytotoxicity (IC50 > 246.02 µM) in vitro. Structure-activity relationship analysis suggested that the trypanocidal activity and cytotoxicity were related to the number of carbons in the aliphatic chain and electronegativity. In vivo experiments, involving oral treatment with nitrofurantoin, showed partial efficacy, whereas the selected analogs showed no treatment efficacy. These results indicate that nitrofurantoin analogs with high hydrophilicity are required for in vivo assessment to determine if they are promising leads for developing trypanocidal drugs.

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Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

et al. 2021

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“…The latter can be distinguished in clathrin-dependent endocytosis, caveolae-dependent endocytosis, macropinocytosis, The ATP assay showed very high versatility and ease-to-use in fact it is used for several different types of nanoparticles like high-density lipoprotein, gold, silver and silica. Furthermore, the use of luminescence as ATP quantification method doesn't show interference with fluorescence/adsorption of nanoparticles Vetten et al, 2013;Cao et al, 2017;Suganuma et al, 2017;Fehaid and Taniguchi, 2019;Silvestri et al, 2019;Wang et al, 2019 Evaluation of NAD + /NADH ratio Luminescence, colorimetry, fluorescence…”

Section: Uptakementioning

confidence: 99%

Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization

Sanità

Carrese

Lamberti

2020

Front. Mol. Biosci.

306

147

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The use of nanoparticles (NP) in diagnosis and treatment of many human diseases, including cancer, is of increasing interest. However, cytotoxic effects of NPs on cells and the uptake efficiency significantly limit their use in clinical practice. The physico-chemical properties of NPs including surface composition, superficial charge, size and shape are considered the key factors that affect the biocompatibility and uptake efficiency of these nanoplatforms. Thanks to the possibility of modifying physico-chemical properties of NPs, it is possible to improve their biocompatibility and uptake efficiency through the functionalization of the NP surface. In this review, we summarize some of the most recent studies in which NP surface modification enhances biocompatibility and uptake. Furthermore, the most used techniques used to assess biocompatibility and uptake are also reported.

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“… a Half-maximal cytotoxic concentration (IC 50 , μM) represented as the mean ± standard deviation (SD), three biological replicates. b Half-maximal inhibitory concentration (IC 50 , μM) represented as the mean ± standard deviation (SD), four biological replicates. c Selectivity index (SI): CC 50 of MDBK/IC 50 of trypanosome. d IC 50 values obtained from the literature. ,, . e MDBK: Madin–Darby bovine kidney cells; Tbb: Trypanosoma brucei brucei ; Tbg: Trypanosoma brucei gambiense ; Tbr: Trypanosoma brucei rhodesiense ; Teq: Trypanosoma equiperdum ; Tev: Trypanosoma evansi; Tc: Trypanosoma congolense ; qualifies as trypanocidal hit if IC 50 ≤ 10 μM and SI ≥ 10 …”

Section: Resultsmentioning

confidence: 99%

In Vitro and In Vivo Trypanocidal Efficacy of Nitrofuryl- and Nitrothienylazines

Janse van Rensburg,

N’Da,

Suganuma

2023

ACS Omega

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African trypanosomiasis is a vector-borne disease of animals and humans in the tsetse fly belt of Africa. Trypanosoma congolense ("nagana") is the most pathogenic trypanosome in livestock and causes high morbidity and mortality rates among cattle. In the absence of effective preventative vaccines, the management of trypanosomiasis relies on chemoprophylaxis and/or -therapy. However, the trypanocides in clinical use exhibit poor oral bioavailability and toxicity, and therapeutic failures occur because of resistant strains. Because nitrofurantoin displayed, in addition to its clinical use, promising antiparasitic activity, the current study was conducted to evaluate the in vitro trypanocidal activity and preliminary in vivo treatment efficacy of previously synthesized nitrofuranylazines. The trypanocidal activity of these nitrofuran derivatives varied among the evaluated trypanosome species; however, T. congolense strain IL3000 was more susceptible than other animal and human trypanosomes. The nitrofurylazines 4a (IC 50 0.04 μM; SI > 7761) and 7a (IC 50 0.03 μM; SI > 9542) as well as the nitrothienylazine 8b (IC 50 0.04 μM; SI 232), with nanomolar IC 50 values, were revealed as early antitrypanosomal leads. Although these derivatives showed strong trypanocidal activity in vitro, no in vivo treatment efficacy was observed in T. congolense IL3000 infected mice after both oral and intraperitoneal administration in a preliminary study. This was attributed to the poor solubility of the test compounds in the in vivo testing media. Indeed, a challenge in drug discovery is finding a balance between the physicochemical properties of a drug candidate, particularly lipophilicity and water solubility, and maintaining adequate potency to provide an effective dose. Hence, future chemical modifications may be required to generate lead-like to lead-like nitrofuranylazines that possess optimal physicochemical and pharmacokinetic properties while retaining in vitro and, ultimately, in vivo trypanocidal efficacy.

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The establishment of in vitro culture and drug screening systems for a newly isolated strain of Trypanosoma equiperdum

Cited by 11 publications

References 18 publications

In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization

In Vitro and In Vivo Trypanocidal Efficacy of Nitrofuryl- and Nitrothienylazines

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