Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host

Abstract

Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.

Parasite, Compartments, and Molecules: Trick versus Treatment on Chagas Disease

“…In this way, the identification of selective targets comprises a logical startpoint to the reduction of the side effects in the hosts [153,163]. Ultrastructural observations can predict the potential primary cellular targets due to their earlier alterations triggered by pharmacologic stimuli, helping the prospection of molecular modes of action of antiparasitic agents [141,174].…”

Design, Synthesis, Trypanocidal Activity, and Studies on Human Albumin Interaction of Novel S-Alkyl-1,2,4-triazoles

“…5,6 Different molecular targets have been investigated, with the aim of developing new alternatives for the treatment of CD. [5][6][7][8] The structural diversity of natural products points out them as an attractive alternative for the development of new and more effective anti-chagasic drugs. 9 Several classes of natural products and their derivatives have shown promising anti T. cruzi activity.…”

“…The trypanocidal activities of the novel derivatives prepared were assessed against the different evolutive forms of T. cruzi as well as their toxic effects against murine macrophages. The novel triazoles were prepared ( Figure 2) with changes in both the substitution at the sulfur atom of the thioether function (4a-4d), 36 and the butadienyl-benzodioxole moiety (5)(6)(7)(8). The new derivatives and analogues were designed to obtain additional information on the SAR for this family of compounds.…”

Síntese de análogos de âncora de GPI: uma contribuição para a descoberta de novos alvos moleculares de Trypanosoma cruzi

“…Moreover, nifurtimox was discontinued in Brazil, because some T. cruzi strains have shown to be resistant to this drug. In summary, all these facts call attention to the urgent search for more selective and specific treatments against Chagas disease (SUETH-SANTIAGO et al, 2017;ANDRADE et al, 1999).…”

“…Antiparasitic chemotherapy is usually based on two classes of targets: the ones that are specific to T. cruzi, and those which are common to parasite and host. In the last case, there must be some selectivity by the bioactive compound for the protozoan's receptors or enzymes, aiming a more significant effect on the parasite and fewer impacts on the host (SUETH-SANTIAGO et al, 2017). In a study performed by Sueth-Santiago and collaborators (2017), T. cruzi's specific targets such as trans-sialidases, trypanothione reductase, and cruzipain have been gaining significant interest in the search for molecules against the parasite in the last two decades.…”