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Rafael Castillo - One of the best experts on this subject based on the ideXlab platform.
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a Benzimidazole Derivative rcb15 in vitro induces the alternative energetic metabolism and glycolysis in taenia crassiceps cysticerci
Acta Tropica, 2017Co-Authors: Guaraciara A Picanco, Rafael Castillo, Javier R Ambrosio, Nayana F Lima, Carolina Miguel Fraga, Tatiane Luiza Da Costa, Eliana Isac, Marina Clare VinaudAbstract:Abstract The emergence of resistance to albendazole has encouraged the search for effective alternatives for cysticercosis and other parasitosis treatment. RCB15 is a Benzimidazole Derivative that may be used against such diseases. The aim of this study was to determine the in vitro effect of RCB15 on the alternative energetic pathways of Taenia crassiceps cysticerci. The cysticerci were in vitro exposed to albendazole sulphoxide (ABZSO) or RCB15 at different concentrations during 24 h. The cysticerci extract and the culture medium were analyzed through spectrophotometry and high performance liquid chromatography as to detect glucose, urea, creatinine and organic acids of the energetic metabolism. The drugs did not influence the protein catabolism. Fatty acids oxidation was enhanced through significantly higher acetate concentrations in the groups treated with RCB15 and ABZSO. Beta-hydroxybutyrate concentrations were decreased which indicates the use of fatty acids towards acetyl-CoA synthesis. There was a decrease in glucose uptake and pyruvate concentrations. The absence of lactate indicates the use of pyruvate in gluconeogenesis. Therefore it is possible to conclude that RCB15 enhanced the alternative energetic pathways of cysticerci in vitro exposed to different concentration, with emphasis on the fatty acids catabolism.
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a Benzimidazole Derivative rcb20 in vitro induces an activation of energetic pathways on taenia crassiceps orf strain cysticerci
Experimental Parasitology, 2017Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole Derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic Benzimidazoles due to a differentiated site of action with similar outcome.
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alternative energy production pathways in taenia crassiceps cysticerci in vitro exposed to a Benzimidazole Derivative rcb20
Parasitology, 2016Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Biochemical studies of Benzimidazole Derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.
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a highly water soluble Benzimidazole Derivative useful for the treatment of fasciolosis
Bioorganic & Medicinal Chemistry Letters, 2014Co-Authors: Miguel Floresramos, Alicia Hernandezcampos, Froylan Ibarravelarde, Yolanda Veramontenegro, Helgi Jungcook, Germinal Jorge Cantoalarcon, Lauro Misael Del Rivero, Rafael CastilloAbstract:This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.
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jvg9 a Benzimidazole Derivative alters the surface and cytoskeleton of trypanosoma cruzi bloodstream trypomastigotes
Memorias Do Instituto Oswaldo Cruz, 2014Co-Authors: Dylan L Diazchiguer, Benjamin Noguedatorres, Alicia Hernandezcampos, Francisco Hernandezluis, Rafael Castillo, Olivia Reynosoducoing, Javier R AmbrosioAbstract:Trypanosoma cruzi has a particular cytoskeleton that consists of a subpellicular network of microtubules and actin microfilaments. Therefore, it is an excellent target for the development of new anti-parasitic drugs. Benzimidazole 2-carbamates, a class of well-known broad-spectrum anthelmintics, have been shown to inhibit the in vitro growth of many protozoa. Therefore, to find efficient anti-trypanosomal (trypanocidal) drugs, our group has designed and synthesised several Benzimidazole Derivatives. One, named JVG9 (5-chloro-1H-Benzimidazole-2-thiol), has been found to be effective against T. cruzi bloodstream trypomastigotes under both in vitro and in vivo conditions. Here, we present the in vitro effects observed by laser scanning confocal and scanning electron microscopy on T. cruzi trypomastigotes. Changes in the surface and the distribution of the cytoskeletal proteins are consistent with the hypothesis that the trypanocidal activity of JVG9 involves the cytoskeleton as a target.
Javier R Ambrosio - One of the best experts on this subject based on the ideXlab platform.
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a Benzimidazole Derivative rcb15 in vitro induces the alternative energetic metabolism and glycolysis in taenia crassiceps cysticerci
Acta Tropica, 2017Co-Authors: Guaraciara A Picanco, Rafael Castillo, Javier R Ambrosio, Nayana F Lima, Carolina Miguel Fraga, Tatiane Luiza Da Costa, Eliana Isac, Marina Clare VinaudAbstract:Abstract The emergence of resistance to albendazole has encouraged the search for effective alternatives for cysticercosis and other parasitosis treatment. RCB15 is a Benzimidazole Derivative that may be used against such diseases. The aim of this study was to determine the in vitro effect of RCB15 on the alternative energetic pathways of Taenia crassiceps cysticerci. The cysticerci were in vitro exposed to albendazole sulphoxide (ABZSO) or RCB15 at different concentrations during 24 h. The cysticerci extract and the culture medium were analyzed through spectrophotometry and high performance liquid chromatography as to detect glucose, urea, creatinine and organic acids of the energetic metabolism. The drugs did not influence the protein catabolism. Fatty acids oxidation was enhanced through significantly higher acetate concentrations in the groups treated with RCB15 and ABZSO. Beta-hydroxybutyrate concentrations were decreased which indicates the use of fatty acids towards acetyl-CoA synthesis. There was a decrease in glucose uptake and pyruvate concentrations. The absence of lactate indicates the use of pyruvate in gluconeogenesis. Therefore it is possible to conclude that RCB15 enhanced the alternative energetic pathways of cysticerci in vitro exposed to different concentration, with emphasis on the fatty acids catabolism.
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a Benzimidazole Derivative rcb20 in vitro induces an activation of energetic pathways on taenia crassiceps orf strain cysticerci
Experimental Parasitology, 2017Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole Derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic Benzimidazoles due to a differentiated site of action with similar outcome.
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alternative energy production pathways in taenia crassiceps cysticerci in vitro exposed to a Benzimidazole Derivative rcb20
Parasitology, 2016Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Biochemical studies of Benzimidazole Derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.
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jvg9 a Benzimidazole Derivative alters the surface and cytoskeleton of trypanosoma cruzi bloodstream trypomastigotes
Memorias Do Instituto Oswaldo Cruz, 2014Co-Authors: Dylan L Diazchiguer, Benjamin Noguedatorres, Alicia Hernandezcampos, Francisco Hernandezluis, Rafael Castillo, Olivia Reynosoducoing, Javier R AmbrosioAbstract:Trypanosoma cruzi has a particular cytoskeleton that consists of a subpellicular network of microtubules and actin microfilaments. Therefore, it is an excellent target for the development of new anti-parasitic drugs. Benzimidazole 2-carbamates, a class of well-known broad-spectrum anthelmintics, have been shown to inhibit the in vitro growth of many protozoa. Therefore, to find efficient anti-trypanosomal (trypanocidal) drugs, our group has designed and synthesised several Benzimidazole Derivatives. One, named JVG9 (5-chloro-1H-Benzimidazole-2-thiol), has been found to be effective against T. cruzi bloodstream trypomastigotes under both in vitro and in vivo conditions. Here, we present the in vitro effects observed by laser scanning confocal and scanning electron microscopy on T. cruzi trypomastigotes. Changes in the surface and the distribution of the cytoskeletal proteins are consistent with the hypothesis that the trypanocidal activity of JVG9 involves the cytoskeleton as a target.
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RCB20, an experimental Benzimidazole Derivative, affects tubulin expression and induces gross anatomical changes in Taenia crassiceps cysticerci
Parasitology Research, 2013Co-Authors: Adrián Márquez-navarro, Rafael Castillo, América Pérez-reyes, Armando Zepeda-rodríguez, Olivia Reynoso-ducoing, Alicia Hernández-campos, Francisco Hernández-luis, Lilian Yépez-mulia, Javier R AmbrosioAbstract:Helminth β-tubulins are the targets of Benzimidazole (BZM) carbamate compounds. The specificity of the interactions between such compounds and their in vivo targets depends on the presence of specific amino acid residues in the target molecules. To discover new and effective anthelmintic drugs, we used a medicinal chemistry approach to synthesize a series of BZM Derivatives that exploited the BZM moiety as a template. We have previously found that one compound, 2-(trifluoromethyl)-1H-Benzimidazole (RCB20), has better in vitro and in vivo activity than albendazole sulfoxide (ABZSO). In the present study, the effect of RCB20 and ABZSO treatment on expression of Taenia crassiceps cysticerci cytoskeletal proteins such as actin, myosin II, and tubulin isoforms was examined. The effects of RCB20 and ABZSO after 11 days treatment of the parasites was evaluated by light, confocal, and electron microscopy, and by immunochemistry and immunohistochemistry. The RCB20-induced effects were more rapid than the ABZSO-induced effects on the parasites. In the RCB20-treated parasites, we observed gross-structural damage at the whole parasite level, particularly in the inner tissues and flame cells. Changes in the expression patterns of the cytoskeletal proteins, as assessed by immunohistochemistry and immunoblotting, revealed that the most important drug-induced effect on the parasites was a reduction in the expression level of tyrosinated α-tubulins. Our research findings suggest that RCB20 treatment affected posttranslational modification of parasite α-tubulin molecules, which involved removal of the α-tubulin carboxy-terminal tyrosine.
Marina Clare Vinaud - One of the best experts on this subject based on the ideXlab platform.
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a Benzimidazole Derivative rcb15 in vitro induces the alternative energetic metabolism and glycolysis in taenia crassiceps cysticerci
Acta Tropica, 2017Co-Authors: Guaraciara A Picanco, Rafael Castillo, Javier R Ambrosio, Nayana F Lima, Carolina Miguel Fraga, Tatiane Luiza Da Costa, Eliana Isac, Marina Clare VinaudAbstract:Abstract The emergence of resistance to albendazole has encouraged the search for effective alternatives for cysticercosis and other parasitosis treatment. RCB15 is a Benzimidazole Derivative that may be used against such diseases. The aim of this study was to determine the in vitro effect of RCB15 on the alternative energetic pathways of Taenia crassiceps cysticerci. The cysticerci were in vitro exposed to albendazole sulphoxide (ABZSO) or RCB15 at different concentrations during 24 h. The cysticerci extract and the culture medium were analyzed through spectrophotometry and high performance liquid chromatography as to detect glucose, urea, creatinine and organic acids of the energetic metabolism. The drugs did not influence the protein catabolism. Fatty acids oxidation was enhanced through significantly higher acetate concentrations in the groups treated with RCB15 and ABZSO. Beta-hydroxybutyrate concentrations were decreased which indicates the use of fatty acids towards acetyl-CoA synthesis. There was a decrease in glucose uptake and pyruvate concentrations. The absence of lactate indicates the use of pyruvate in gluconeogenesis. Therefore it is possible to conclude that RCB15 enhanced the alternative energetic pathways of cysticerci in vitro exposed to different concentration, with emphasis on the fatty acids catabolism.
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a Benzimidazole Derivative rcb20 in vitro induces an activation of energetic pathways on taenia crassiceps orf strain cysticerci
Experimental Parasitology, 2017Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole Derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic Benzimidazoles due to a differentiated site of action with similar outcome.
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alternative energy production pathways in taenia crassiceps cysticerci in vitro exposed to a Benzimidazole Derivative rcb20
Parasitology, 2016Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Biochemical studies of Benzimidazole Derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.
Alicia Hernandezcampos - One of the best experts on this subject based on the ideXlab platform.
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a Benzimidazole Derivative rcb20 in vitro induces an activation of energetic pathways on taenia crassiceps orf strain cysticerci
Experimental Parasitology, 2017Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole Derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic Benzimidazoles due to a differentiated site of action with similar outcome.
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alternative energy production pathways in taenia crassiceps cysticerci in vitro exposed to a Benzimidazole Derivative rcb20
Parasitology, 2016Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Biochemical studies of Benzimidazole Derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.
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a highly water soluble Benzimidazole Derivative useful for the treatment of fasciolosis
Bioorganic & Medicinal Chemistry Letters, 2014Co-Authors: Miguel Floresramos, Alicia Hernandezcampos, Froylan Ibarravelarde, Yolanda Veramontenegro, Helgi Jungcook, Germinal Jorge Cantoalarcon, Lauro Misael Del Rivero, Rafael CastilloAbstract:This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.
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jvg9 a Benzimidazole Derivative alters the surface and cytoskeleton of trypanosoma cruzi bloodstream trypomastigotes
Memorias Do Instituto Oswaldo Cruz, 2014Co-Authors: Dylan L Diazchiguer, Benjamin Noguedatorres, Alicia Hernandezcampos, Francisco Hernandezluis, Rafael Castillo, Olivia Reynosoducoing, Javier R AmbrosioAbstract:Trypanosoma cruzi has a particular cytoskeleton that consists of a subpellicular network of microtubules and actin microfilaments. Therefore, it is an excellent target for the development of new anti-parasitic drugs. Benzimidazole 2-carbamates, a class of well-known broad-spectrum anthelmintics, have been shown to inhibit the in vitro growth of many protozoa. Therefore, to find efficient anti-trypanosomal (trypanocidal) drugs, our group has designed and synthesised several Benzimidazole Derivatives. One, named JVG9 (5-chloro-1H-Benzimidazole-2-thiol), has been found to be effective against T. cruzi bloodstream trypomastigotes under both in vitro and in vivo conditions. Here, we present the in vitro effects observed by laser scanning confocal and scanning electron microscopy on T. cruzi trypomastigotes. Changes in the surface and the distribution of the cytoskeletal proteins are consistent with the hypothesis that the trypanocidal activity of JVG9 involves the cytoskeleton as a target.
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analysis of the effect of a 2 trifluoromethyl 1h Benzimidazole Derivative on trichinella spiralis muscle larvae
Veterinary Parasitology, 2013Co-Authors: Felix Matadamasmartinez, Benjamin Noguedatorres, Alicia Hernandezcampos, Francisco Hernandezluis, Rafael Castillo, Guillermo Mendoza, Javier R Ambrosio, Gabriela Andresantonio, Lilian YepezmuliaAbstract:Albendazole and mebendazole are widely used in the treatment of trichinellosis; however, chemotherapy failure has been reported. In an effort to develop new anthelminthic compounds, we examined a previously synthesized 2-(trifluoromethyl)-1H-Benzimidazole Derivative (1) that showed good in vitro activity against Trichinella spiralis muscle larvae but low in vivo efficacy. In order to improve the solubility of compound 1, an inclusion complex with 2-hydroxypropyl-β-cyclodextrin (1/HP-βCD) was prepared. When 1/HP-βCD was tested in vivo, it significantly reduced the ML burden (84%). In addition, a proteomic analysis of T. spiralis ML treated with 1 revealed significant changes in the expression levels of proteins involved in energy metabolism and the cytoskeleton of the parasite. Compound (1) also induced extensive ultrastructural changes in the cuticle, hypodermis and midgut of the parasite.
Carolina Miguel Fraga - One of the best experts on this subject based on the ideXlab platform.
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a Benzimidazole Derivative rcb15 in vitro induces the alternative energetic metabolism and glycolysis in taenia crassiceps cysticerci
Acta Tropica, 2017Co-Authors: Guaraciara A Picanco, Rafael Castillo, Javier R Ambrosio, Nayana F Lima, Carolina Miguel Fraga, Tatiane Luiza Da Costa, Eliana Isac, Marina Clare VinaudAbstract:Abstract The emergence of resistance to albendazole has encouraged the search for effective alternatives for cysticercosis and other parasitosis treatment. RCB15 is a Benzimidazole Derivative that may be used against such diseases. The aim of this study was to determine the in vitro effect of RCB15 on the alternative energetic pathways of Taenia crassiceps cysticerci. The cysticerci were in vitro exposed to albendazole sulphoxide (ABZSO) or RCB15 at different concentrations during 24 h. The cysticerci extract and the culture medium were analyzed through spectrophotometry and high performance liquid chromatography as to detect glucose, urea, creatinine and organic acids of the energetic metabolism. The drugs did not influence the protein catabolism. Fatty acids oxidation was enhanced through significantly higher acetate concentrations in the groups treated with RCB15 and ABZSO. Beta-hydroxybutyrate concentrations were decreased which indicates the use of fatty acids towards acetyl-CoA synthesis. There was a decrease in glucose uptake and pyruvate concentrations. The absence of lactate indicates the use of pyruvate in gluconeogenesis. Therefore it is possible to conclude that RCB15 enhanced the alternative energetic pathways of cysticerci in vitro exposed to different concentration, with emphasis on the fatty acids catabolism.
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a Benzimidazole Derivative rcb20 in vitro induces an activation of energetic pathways on taenia crassiceps orf strain cysticerci
Experimental Parasitology, 2017Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole Derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic Benzimidazoles due to a differentiated site of action with similar outcome.
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alternative energy production pathways in taenia crassiceps cysticerci in vitro exposed to a Benzimidazole Derivative rcb20
Parasitology, 2016Co-Authors: Carolina Miguel Fraga, Alicia Hernandezcampos, Rafael Castillo, Javier R Ambrosio, Tatiane Luiza Da Costa, Ana Maria De Castro, Olivia Reynosoducoing, Marina Clare VinaudAbstract:Biochemical studies of Benzimidazole Derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-Benzimidazole (RCB20) is a Benzimidazole Derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.