The thiol-polyamine metabolism of Trypanosoma cruzi: molecular targets and drug repurposing strategies

TALEVI A; CARRILLO C; COMINI M

CURRENT MEDICINAL CHEMISTRY.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2019

0929-8673

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 ofparasite biology and host-pathogen interaction has not been paralleled by the development of novel, safe and effective therapeuticoptions. It is then urgent to seek for novel therapeutic candidates and to implement drug discovery strategies that may accelerate thediscovery process. The most appealing targets for pharmacological intervention are those essential for the pathogen and, wheneverpossible, absent or significantly different from the host homologue. The thiol-polyamine metabolism of T. cruzi offers interestingcandidates for a rational design of selective drugs. In this respect, here we critically review the state of the art of the thiol-polyaminemetabolism of T. cruzi and the pharmacological potential of its components. On the other hand, drug repurposing emerged as a validstrategy to identify new biological activities for drugs in clinical use, while significantly shortening the long time and high costassociated with de novo drug discovery approaches. Thus, we also discuss the different drug repurposing strategies available withspecial emphasis in its application to the identification of drug candidates targeting essential components of the thiol-polyaminemetabolism of T. cruzi.