New Therapeutic Targets for Drug Design Against Trypanosoma cruzi, Advances and Perspectives

Abstract

Chagas disease is one of the most important parasitic diseases in Latin America, affecting 16 to 18 million people. Nifurtimox and Benznidazol are drugs that are commonly used in its treatment; however, these drugs produce several adverse reactions and are not effective in the chronic phase of the disease. Therefore, the design, synthesis, and biological evaluation of new compounds with potential activity against Trypanozoma cruzi are of great importance. We review six proteins involved in the biochemical metabolism of Trypanosoma cruzi that have recently been studied as potential targets for designing new drugs for Chagas disease. These are farnesyl pyrophosphate synthase, trans-sialidase, cruzain cystein protease, trypanothione reductase, glucose 6-phosphate-dehydrogenase, glyceraldehyde 3-phosphate-dehydrogenase, and alpha-hydroxy acid dehydrogenase. We also review the advances of compounds recently designed based on structure-activity, and the perspectives of new compounds that inhibit these therapeutic targets.

Effect of complexation of 3-aminoquinoxaline-2-carbonitrile 1,4-dioxides with palladium and copper on their anti-T. cruzi activity

“…For these reasons the development of more safe and efficient drugs against Chagas' disease is urgent (Nwaka and Ridley, 2003). Several types of compounds have been described as anti-T. cruzi agents acting on different biological targets (Rivera et al, 2009). Some quinoxaline derivatives were carefully selected from Dr. Antonio Monge chemical-library in order to evaluate them against T. cruzi being 3-aminosubstituted-2-carbonitrile derivatives (i.e., 1 and 2, Fig.…”

High Throughput Screening against the Peroxidase Cascade of African Trypanosomes Identifies Antiparasitic Compounds That Inactivate Tryparedoxin

“…The dithiol is kept reduced by NADPH and the flavoenzyme trypanothione reductase (TR), the system replacing the glutathione/glutathione reductase couple of the mammalian host (4). TR is the most thoroughly studied enzyme of the trypanothione metabolism, and a large number of inhibitors has been identified (5)(6)(7)(8)(9). Tpx is a distant member of the thioredoxin (Trx) protein family.…”

Online fast Biospeckle monitoring of drug action in Trypanosoma cruzi parasites by motion history image

“…The available drugs for the specific treatment of the infection by T. cruzi are nifurtimox and benznidazole [16]. Long follow-up is necessary, and both drugs are not devoid of side effects, nor are they effective in all treated cases.…”