1. The Thiol-polyamine Metabolism of Trypanosoma cruzi: Molecular Targets and Drug Repurposing Strategies
- Author
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Carolina Carrillo, Alan Talevi, and Marcelo A. Comini
- Subjects
TRYPANOTHIONE ,0301 basic medicine ,Spermidine ,Trypanothione ,Disease ,DRUG REPOSITIONING ,THERAPY ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,Polyamines ,Medicine ,media_common ,biology ,Drug discovery ,BIOINFORMATICS ,Bioquímica y Biología Molecular ,CHAGAS´ DISEASE ,Glutathione ,Trypanocidal Agents ,Antidepressive Agents ,Drug repositioning ,DRUG REPURPOSING ,Molecular Medicine ,Identification (biology) ,CIENCIAS NATURALES Y EXACTAS ,Antipsychotic Agents ,Drug ,Trypanosoma cruzi ,media_common.quotation_subject ,030231 tropical medicine ,APPROVED DRUGS ,Computational biology ,SPERMIDINE ,Ciencias Biológicas ,03 medical and health sciences ,Animals ,Humans ,Sulfhydryl Compounds ,Pharmacology ,business.industry ,Organic Chemistry ,Drug Repositioning ,Rational design ,biology.organism_classification ,SCREENING ,POLYAMINES ,030104 developmental biology ,chemistry ,business - Abstract
Chagas´ disease continues to be a challenging and neglected public health problem in many American countries. The etiologic agent, Trypanosoma cruzi, develops intracellularly in the mammalian host, which hinders treatment efficacy. Progress in the knowledge of parasite biology and host-pathogen interaction has not been paralleled by the development of novel, safe and effective therapeutic options. It is then urgent to seek for novel therapeutic candidates and to implement drug discovery strategies that may accelerate the discovery process. The most appealing targets for pharmacological intervention are those essential for the pathogen and, whenever possible, absent or significantly different from the host homolog. The thiol-polyamine metabolism of T. cruzi offers interesting candidates for a rational design of selective drugs. In this respect, here we critically review the state of the art of the thiolpolyamine metabolism of T. cruzi and the pharmacological potential of its components. On the other hand, drug repurposing emerged as a valid strategy to identify new biological activities for drugs in clinical use, while significantly shortening the long time and high cost associated with de novo drug discovery approaches. Thus, we also discuss the different drug repurposing strategies available with a special emphasis in their applications to the identification of drug candidates targeting essential components of the thiol-polyamine metabolism of T. cruzi. Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: 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"; Argentina Fil: Comini, Marcelo. Instituto Pasteur de Montevideo; Uruguay
- Published
- 2019
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