The Experts below are selected from a list of 462 Experts worldwide ranked by ideXlab platform

Mariana Bonilla - One of the best experts on this subject based on the ideXlab platform.

  • Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites
    2016
    Co-Authors: Fabiana Ross, Williams Porcal, Gloria V. López, Hugo Cerecetto, Tatiana Basika, Carlos Carmona, Gabriela Maggioli, Mariana Bonilla, Vadim N. Gladyshev, Mariana Boiani
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 mM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, an

  • identification of thioredoxin glutathione reductase inhibitors that kill cestode and trematode parasites
    PLOS ONE, 2012
    Co-Authors: Fabiana Ross, Williams Porcal, Hugo Cerecetto, Tatiana Basika, Gabriela Maggioli, Paola Hernandez, Gloria V Lopez, Mercedes Gonzalez, Carlos P Carmona, Mariana Bonilla
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified Phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites.

Fabiana Ross - One of the best experts on this subject based on the ideXlab platform.

  • Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites
    2016
    Co-Authors: Fabiana Ross, Williams Porcal, Gloria V. López, Hugo Cerecetto, Tatiana Basika, Carlos Carmona, Gabriela Maggioli, Mariana Bonilla, Vadim N. Gladyshev, Mariana Boiani
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 mM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, an

  • identification of thioredoxin glutathione reductase inhibitors that kill cestode and trematode parasites
    PLOS ONE, 2012
    Co-Authors: Fabiana Ross, Williams Porcal, Hugo Cerecetto, Tatiana Basika, Gabriela Maggioli, Paola Hernandez, Gloria V Lopez, Mercedes Gonzalez, Carlos P Carmona, Mariana Bonilla
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified Phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites.

David Crich - One of the best experts on this subject based on the ideXlab platform.

  • Cyclic Tautomers of Tryptophan: Enantio- and Diastereoselective Synthesis of .beta.-Substituted and .alpha.,.beta.-Disubstituted Derivatives of Tryptophan
    The Journal of Organic Chemistry, 1994
    Co-Authors: Milan Bruncko, David Crich
    Abstract:

    A method is presented for the synthesis of enantiomerically pure erythro-β-alkylated derivatives of L-tryptophan from L-tryptophan itself via the intermediacy of cyclic tryptophan tautomers. Dehydrogenation of the cyclic tryptophan tautomer 2 to 3 is achieved via either the 2-phenylseleno derivative 6 or its 2-phenylthio counterpart 7 by oxidation to the corresponding selenoxide or sulfoxide and formal syn-elimination. Evidence is provided that this elimination proceeds, at least in part, by a stepwise rather than a concerted pericyclic mechanism. Soft nucleophiles, including thiolates, amines, and higher order cuprates, add to 3 in conjugate fashion in high yield and with excellent diastereoselectivity from the exo-face of the bicyclic system. The enolate anion resulting from conjugate addition is likewise quenched with high selectivity from the exo face either by simple protonation or by alkylation with methyl iodide. The tetrahydropyrroloindole 3 also reacts with cyclopentadiene in a Dields-Alder reaction with excellent selectivity to give 29. Sulfur ylide chemistry enables the formation of the cyclopropane adduct 27. After conjuguate addition, cycloreversion to the tryptophan skeleton is achieved by dissolution in trifluoroacetic acid. The rate of ring opening is strongly dependant on the steric bulk and orientation of the substituenet at C-3, with large exo-substituents strongly retarding ring opening and endo-substituents favoring ring opening. Desulfonylation is achieved by photolysis with ascorbic acid and anisole and final deprotection by heating to reflux with 6 M hydrchloric acid. Desulfonylation of the 2,3-methano derivative 37 resulted in degradation of the cyclopropane ring. Use of a (4-methoxyphenyl)sulfonyl Group in place of the Phenylsulfonyl Group, as in 11 and 22, enables one-step desulfonylation and ring opening by treatment with methanesulfonic acid

Williams Porcal - One of the best experts on this subject based on the ideXlab platform.

  • Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites
    2016
    Co-Authors: Fabiana Ross, Williams Porcal, Gloria V. López, Hugo Cerecetto, Tatiana Basika, Carlos Carmona, Gabriela Maggioli, Mariana Bonilla, Vadim N. Gladyshev, Mariana Boiani
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 mM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, an

  • identification of thioredoxin glutathione reductase inhibitors that kill cestode and trematode parasites
    PLOS ONE, 2012
    Co-Authors: Fabiana Ross, Williams Porcal, Hugo Cerecetto, Tatiana Basika, Gabriela Maggioli, Paola Hernandez, Gloria V Lopez, Mercedes Gonzalez, Carlos P Carmona, Mariana Bonilla
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified Phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites.

Hugo Cerecetto - One of the best experts on this subject based on the ideXlab platform.

  • Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites
    2016
    Co-Authors: Fabiana Ross, Williams Porcal, Gloria V. López, Hugo Cerecetto, Tatiana Basika, Carlos Carmona, Gabriela Maggioli, Mariana Bonilla, Vadim N. Gladyshev, Mariana Boiani
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 mM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, an

  • identification of thioredoxin glutathione reductase inhibitors that kill cestode and trematode parasites
    PLOS ONE, 2012
    Co-Authors: Fabiana Ross, Williams Porcal, Hugo Cerecetto, Tatiana Basika, Gabriela Maggioli, Paola Hernandez, Gloria V Lopez, Mercedes Gonzalez, Carlos P Carmona, Mariana Bonilla
    Abstract:

    Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a Phenylsulfonyl Group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified Phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites.