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Carolina Carrillo - One of the best experts on this subject based on the ideXlab platform.
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Data_Sheet_2_Cascade Ligand- and Structure-Based Virtual Screening to Identify New Trypanocidal Compounds Inhibiting Putrescine Uptake.XLSX
2018Co-Authors: Lucas N. Alberca, María L. Sbaraglini, Juan F. Morales, Roque Dietrich, María D. Ruiz, Agustina Pino M. Martínez, Cristian G. Miranda, Laura Fraccaroli, Catalina Alba D. Soto, Carolina CarrilloAbstract:Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001–0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and Butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.
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Cascade Ligand- and Structure-Based Virtual Screening to Identify New Trypanocidal Compounds Inhibiting Putrescine Uptake
Frontiers Media S.A., 2018Co-Authors: Lucas N. Alberca, María L. Sbaraglini, Juan F. Morales, Roque Dietrich, María D. Ruiz, Agustina Pino M. Martínez, Cristian G. Miranda, Laura Fraccaroli, Catalina Alba D. Soto, Carolina CarrilloAbstract:Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001–0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and Butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake
Jack D Sobel - One of the best experts on this subject based on the ideXlab platform.
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comparative in vitro activity of antimycotic agents against pathogenic vaginal yeast isolates
Medical Mycology, 1994Co-Authors: M E Lynch, Jack D SobelAbstract:Although numerous antimycotic agents are available for the treatment of yeast vaginitis there is little comparative data on the in vitro activity of these drugs. In the present two-part study, in vitro macro-broth dilution sensitivity tests were performed on a total of 377 clinical vaginal yeast isolates of nine different species. Antimycotics surveyed included amphotericin B, 5-fluorocytosine and eight azole derivatives. Results show that all vaginal Candida albicans isolates were uniformly sensitive at low concentration to all 10 antimycotics tested. However, non-albicans species, especially Candida glabrata and Saccharomyces cerevisiae, manifested several-fold increases in minimal inhibitory concentrations to all azoles tested except Butoconazole. In particular, the in vitro potency of fluconazole and terconazole against species other than C. albicans was relatively poor, whereas the drugs demonstrating the best activity were itraconazole, Butoconazole and saperconazole. Susceptibility testing of vaginal C. albicans isolates is not routinely indicated, even in patients with recurrent vaginitis and should be reserved for selected organisms, especially non-albicans species, in patients with clinical failure only.
Carrillo Carolina - One of the best experts on this subject based on the ideXlab platform.
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Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
'Frontiers Media SA', 2020Co-Authors: Alberca, Lucas Nicolás, Sbaraglini, María Laura, Morales, Juan Francisco, Dietrich, Roque Carlos, Ruiz, María Daniela, Pino Martínez, Agustina María, Miranda, Cristian Gabriel, Fraccaroli, Laura Virginia, Alba Soto, Catalina Dirney, Carrillo CarolinaAbstract:Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and Butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.Facultad de Ciencias ExactasLaboratorio de Investigación y Desarrollo de Bioactivo
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Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
'Frontiers Media SA', 2018Co-Authors: Alberca, Lucas Nicolás, Sbaraglini, María Laura, Morales, Juan Francisco, Dietrich, Roque Carlos, Ruiz, María Daniela, Pino Martínez, Agustina María, Miranda, Cristian Gabriel, Fraccaroli, Laura Virginia, Alba Soto, Catalina Dirney, Carrillo CarolinaAbstract:Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and Butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.Fil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Morales, Juan Francisco. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Dietrich, Roque Carlos. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Ruiz, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Pino Martínez, Agustina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Miranda, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Palestro, Pablo Hernán. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentin
Campbell K. Skokos - One of the best experts on this subject based on the ideXlab platform.
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An Evaluation of Butoconazole Nitrate 2% Site Release® Vaginal Cream (Gynazole-1®) Compared to Fluconazole 150 mg Tablets (Diflucan®) in the Time to Relief of Symptoms in Patients With Vulvovaginal Candidiasis
Hindawi Limited, 2005Co-Authors: Larry S. Seidman, Campbell K. SkokosAbstract:Background. It is estimated that as many as 13 million cases of vulvovaginal infection occur in the United States annually, the majority of which are the result of Candida albicans infection. The symptoms of vulvovaginal infections are often painful and distressing to the patient. The objective of this study was to compare the time to symptomatic relief of vulvovaginal candidiasis (VVC) with Butoconazole nitrate 2% Site Release® vaginal cream (Gynazole-1®) and oral fluconazole 150 mg tablets (Diflucan®)
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An Evaluation of Butoconazole Nitrate 2% Site Release® Vaginal Cream (Gynazole-1®) Compared to Fluconazole 150 mg Tablets (Diflucan®) in the Time to Relief of Symptoms in Patients With Vulvovaginal Candidiasis
Hindawi Limited, 2005Co-Authors: Campbell K. Skokos, Larry S. SeidmanAbstract:Background. It is estimated that as many as 13 million cases of vulvovaginal infection occur in the United States annually, the majority of which are the result of Candida albicans infection. The symptoms of vulvovaginal infections are often painful and distressing to the patient. The objective of this study was to compare the time to symptomatic relief of vulvovaginal candidiasis (VVC) with Butoconazole nitrate 2% Site Release® vaginal cream (Gynazole-1®) and oral fluconazole 150 mg tablets (Diflucan®)
Larry S. Seidman - One of the best experts on this subject based on the ideXlab platform.
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An Evaluation of Butoconazole Nitrate 2% Site Release® Vaginal Cream (Gynazole-1®) Compared to Fluconazole 150 mg Tablets (Diflucan®) in the Time to Relief of Symptoms in Patients With Vulvovaginal Candidiasis
Hindawi Limited, 2005Co-Authors: Larry S. Seidman, Campbell K. SkokosAbstract:Background. It is estimated that as many as 13 million cases of vulvovaginal infection occur in the United States annually, the majority of which are the result of Candida albicans infection. The symptoms of vulvovaginal infections are often painful and distressing to the patient. The objective of this study was to compare the time to symptomatic relief of vulvovaginal candidiasis (VVC) with Butoconazole nitrate 2% Site Release® vaginal cream (Gynazole-1®) and oral fluconazole 150 mg tablets (Diflucan®)
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An Evaluation of Butoconazole Nitrate 2% Site Release® Vaginal Cream (Gynazole-1®) Compared to Fluconazole 150 mg Tablets (Diflucan®) in the Time to Relief of Symptoms in Patients With Vulvovaginal Candidiasis
Hindawi Limited, 2005Co-Authors: Campbell K. Skokos, Larry S. SeidmanAbstract:Background. It is estimated that as many as 13 million cases of vulvovaginal infection occur in the United States annually, the majority of which are the result of Candida albicans infection. The symptoms of vulvovaginal infections are often painful and distressing to the patient. The objective of this study was to compare the time to symptomatic relief of vulvovaginal candidiasis (VVC) with Butoconazole nitrate 2% Site Release® vaginal cream (Gynazole-1®) and oral fluconazole 150 mg tablets (Diflucan®)
