The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Theresa H.t. Coetzer - One of the best experts on this subject based on the ideXlab platform.
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Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei.
Experimental Parasitology, 1999Co-Authors: Linda Troeberg, James T. Palmer, John D. Lonsdale-eccles, Rory E. Morty, Robert N. Pike, James H Mckerrow, Theresa H.t. CoetzerAbstract:Abstract Troeberg, L., Morty, R. E., Pike, R. N., Lonsdale-Eccles, J. D., Palmer, J. T., McKerrow, J. H., and Coetzer, T. H. T. 1999. Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei. Experimental Parasitology 91 , 349–355. Trypanosoma brucei brucei is a causative Agent of bovine trypanosomiasis (nagana), a disease of considerable economic significance in much of Africa. Here we report investigations on the effects of various irreversible cysteine proteinase inhibitors, including vinyl sulfones (VS), peptidyl chloromethylketones (CMK), diazomethylketones, and fluoromethyl ketones, on the major lysosomal cysteine proteinase (trypanopain-Tb) of T. b. brucei and on in vitro -cultured bloodstream forms of the parasite. Many of the tested inhibitors were Trypanocidal at low micromolar concentrations. Methylpiperazine urea-Phe-homoPhe-VS was the most effective Trypanocidal Agent, killing 50% of test populations at a work ing concentration of 0.11 μM, while carbobenzoxy-Phe-Phe-CMK was the most Trypanocidal of the methylketones with an IC 50 of 3.6 μM. Labelling of live and lysed T. b. brucei with biotinylated inhibitor derivatives suggests that trypanopain-Tb is the likely intracellular target for these inhibitors. Kinetic analysis of the inhibition of purified trypanopain-Tb by the inhibitors showed that most had k ass values in the 10 6 M −1 s −1 range. We conclude that cysteine proteinase inhibitors have potential as Trypanocidal Agents and that a major target of these compounds is the lysosomal enzyme trypanopain-Tb.
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Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei.
Experimental parasitology, 1999Co-Authors: Linda Troeberg, James T. Palmer, John D. Lonsdale-eccles, Rory E. Morty, Robert N. Pike, James H Mckerrow, Theresa H.t. CoetzerAbstract:Trypanosoma brucei brucei is a causative Agent of bovine trypanosomiasis (nagana), a disease of considerable economic significance in much of Africa. Here we report investigations on the effects of various irreversible cysteine proteinase inhibitors, including vinyl sulfones (VS), peptidyl chloromethylketones (CMK), diazomethylketones, and fluoromethyl ketones, on the major lysosomal cysteine proteinase (trypanopain-Tb) of T. b. brucei and on in vitro-cultured bloodstream forms of the parasite. Many of the tested inhibitors were Trypanocidal at low micromolar concentrations. Methylpiperazine urea-Phe-homoPhe-VS was the most effective Trypanocidal Agent, killing 50% of test populations at a work ing concentration of 0.11 microM, while carbobenzoxy-Phe-Phe-CMK was the most Trypanocidal of the methylketones with an IC50 of 3.6 microM. Labelling of live and lysed T. b. brucei with biotinylated inhibitor derivatives suggests that trypanopain-Tb is the likely intracellular target for these inhibitors. Kinetic analysis of the inhibition of purified trypanopain-Tb by the inhibitors showed that most had kass values in the 10(6) M-1 s-1 range. We conclude that cysteine proteinase inhibitors have potential as Trypanocidal Agents and that a major target of these compounds is the lysosomal enzyme trypanopain-Tb.
Fredrik Björkling - One of the best experts on this subject based on the ideXlab platform.
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Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei
Bioorganic & medicinal chemistry letters, 2012Co-Authors: John M. Kelly, Martin C. Taylor, David Horn, Einars Loza, Ivars Kalvinsh, Fredrik BjörklingAbstract:A number of hydroxamic acid derivatives which inhibit human histone deacetylases were investigated for efficacy against cultured bloodstream form Trypanosoma brucei. Three out of the four classes tested displayed significant activity. The majority of compounds blocked parasite growth in the submicromolar range. The most potent was a member of the sulphonepiperazine series with an IC50 of 34 nM. These results identify lead compounds with potential for the development of a novel class of Trypanocidal Agent.
Zumira A. Carneiro - One of the best experts on this subject based on the ideXlab platform.
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Development and Evaluation of a Nanoemulsion Containing Ursolic Acid: a Promising Trypanocidal Agent : Nanoemulsion with Ursolic Acid Against T. cruzi
AAPS PharmSciTech, 2017Co-Authors: Erika Cristina Vargas De Oliveira, Sérgio Albuquerque, Zumira A. Carneiro, Juliana Maldonado MarchettiAbstract:Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good Trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its Trypanocidal activity and cytotoxicity evaluated. Pseudo-ternary phase diagrams and hydrophilic-lipophilic balance (HLB) system were used in the development. The system was stable throughout 90 days of testing, as evidenced by turbidimetry analysis and measurements of the droplet size (57.3 nm) and polydispersity index (0.24). Fourier transform infrared spectroscopy and mass spectrometry evidenced drug’s integrity in the formulation. An in vitro dissolution profile showed 75% of ursolic acid release after 5 min from the nanoemulsion into the alkaline dissolution medium, while only 20% could be released from a physical mixture after 2 h. Trypanocidal activity and cytotoxicity were evaluated on the CL Brener strain and LLC-MK2 (monkey kidney) fibroblast by chlorophenol red-β-d-galactoside (CPRG) method. Biological studies showed that the developed formulation was nontoxic and effective against replicant forms of the parasite. A stable and efficient nanoemulsion could be developed to improve the delivery of a promising drug to treat a threatening illness such as Chagas disease.
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In vitro and in vivo Trypanocidal activity of H2bdtc-loaded solid lipid nanoparticles
PLoS neglected tropical diseases, 2014Co-Authors: Zumira A. Carneiro, Pedro I. S. Maia, Renata Sesti-costa, Carla D. Lopes, Tatiana A. Pereira, Cristiane M. Milanezi, Marcelo Da Silva, Renata Fonseca Vianna Lopez, João Santana Da Silva, Victor M. DeflonAbstract:The parasite Trypanosoma cruzi causes Chagas disease, which remains a serious public health concern and continues to victimize thousands of people, primarily in the poorest regions of Latin America. In the search for new therapeutic drugs against T. cruzi, here we have evaluated both the in vitro and the in vivo activity of 5-hydroxy-3-methyl-5-phenyl-pyrazoline-1-(S-benzyl dithiocarbazate) (H2bdtc) as a free compound or encapsulated into solid lipid nanoparticles (SLN); we compared the results with those achieved by using the currently employed drug, benznidazole. H2bdtc encapsulated into solid lipid nanoparticles (a) effectively reduced parasitemia in mice at concentrations 100 times lower than that normally employed for benznidazole (clinically applied at a concentration of 400 µmol kg−1 day−1); (b) diminished inflammation and lesions of the liver and heart; and (c) resulted in 100% survival of mice infected with T. cruzi. Therefore, H2bdtc is a potent Trypanocidal Agent.
Linda Troeberg - One of the best experts on this subject based on the ideXlab platform.
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Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei.
Experimental Parasitology, 1999Co-Authors: Linda Troeberg, James T. Palmer, John D. Lonsdale-eccles, Rory E. Morty, Robert N. Pike, James H Mckerrow, Theresa H.t. CoetzerAbstract:Abstract Troeberg, L., Morty, R. E., Pike, R. N., Lonsdale-Eccles, J. D., Palmer, J. T., McKerrow, J. H., and Coetzer, T. H. T. 1999. Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei. Experimental Parasitology 91 , 349–355. Trypanosoma brucei brucei is a causative Agent of bovine trypanosomiasis (nagana), a disease of considerable economic significance in much of Africa. Here we report investigations on the effects of various irreversible cysteine proteinase inhibitors, including vinyl sulfones (VS), peptidyl chloromethylketones (CMK), diazomethylketones, and fluoromethyl ketones, on the major lysosomal cysteine proteinase (trypanopain-Tb) of T. b. brucei and on in vitro -cultured bloodstream forms of the parasite. Many of the tested inhibitors were Trypanocidal at low micromolar concentrations. Methylpiperazine urea-Phe-homoPhe-VS was the most effective Trypanocidal Agent, killing 50% of test populations at a work ing concentration of 0.11 μM, while carbobenzoxy-Phe-Phe-CMK was the most Trypanocidal of the methylketones with an IC 50 of 3.6 μM. Labelling of live and lysed T. b. brucei with biotinylated inhibitor derivatives suggests that trypanopain-Tb is the likely intracellular target for these inhibitors. Kinetic analysis of the inhibition of purified trypanopain-Tb by the inhibitors showed that most had k ass values in the 10 6 M −1 s −1 range. We conclude that cysteine proteinase inhibitors have potential as Trypanocidal Agents and that a major target of these compounds is the lysosomal enzyme trypanopain-Tb.
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Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei.
Experimental parasitology, 1999Co-Authors: Linda Troeberg, James T. Palmer, John D. Lonsdale-eccles, Rory E. Morty, Robert N. Pike, James H Mckerrow, Theresa H.t. CoetzerAbstract:Trypanosoma brucei brucei is a causative Agent of bovine trypanosomiasis (nagana), a disease of considerable economic significance in much of Africa. Here we report investigations on the effects of various irreversible cysteine proteinase inhibitors, including vinyl sulfones (VS), peptidyl chloromethylketones (CMK), diazomethylketones, and fluoromethyl ketones, on the major lysosomal cysteine proteinase (trypanopain-Tb) of T. b. brucei and on in vitro-cultured bloodstream forms of the parasite. Many of the tested inhibitors were Trypanocidal at low micromolar concentrations. Methylpiperazine urea-Phe-homoPhe-VS was the most effective Trypanocidal Agent, killing 50% of test populations at a work ing concentration of 0.11 microM, while carbobenzoxy-Phe-Phe-CMK was the most Trypanocidal of the methylketones with an IC50 of 3.6 microM. Labelling of live and lysed T. b. brucei with biotinylated inhibitor derivatives suggests that trypanopain-Tb is the likely intracellular target for these inhibitors. Kinetic analysis of the inhibition of purified trypanopain-Tb by the inhibitors showed that most had kass values in the 10(6) M-1 s-1 range. We conclude that cysteine proteinase inhibitors have potential as Trypanocidal Agents and that a major target of these compounds is the lysosomal enzyme trypanopain-Tb.
John M. Kelly - One of the best experts on this subject based on the ideXlab platform.
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Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei
Bioorganic & medicinal chemistry letters, 2012Co-Authors: John M. Kelly, Martin C. Taylor, David Horn, Einars Loza, Ivars Kalvinsh, Fredrik BjörklingAbstract:A number of hydroxamic acid derivatives which inhibit human histone deacetylases were investigated for efficacy against cultured bloodstream form Trypanosoma brucei. Three out of the four classes tested displayed significant activity. The majority of compounds blocked parasite growth in the submicromolar range. The most potent was a member of the sulphonepiperazine series with an IC50 of 34 nM. These results identify lead compounds with potential for the development of a novel class of Trypanocidal Agent.
