Cruzain Inhibitors as Prominent Molecules with The Potential to become Drug Candidates against Chagas Disease

Chagas disease, a parasitic, endemic infection affects about 10–15 million of people all over Latin America. In addition, Chagas disease has an increased global impact in nonendemic areas due to immigration patterns. More than 10, 000 deaths are caused by this disease each year, and nearly 70 million people are susceptible to infection. Although Chagas disease was identified more than 100 years ago, current therapeutic options for this condition are limited mainly to two ineffective drugs, benznidazole and nifurtimox. These two drugs are not optimal as currently applied because they show substantial toxicity, require long courses of administration and have inconsistent efficacy. In light of these problems, safer and more effective therapeutic options for patients with Chagas disease are clearly needed. Many candidate drugs are currently being tested. Among them, cruzapain inhibitors are considered promising agents that have been shown to have potential for more effective treatment of the chronic form of Chagas disease. In this work we review briefly the most significant advance in the design of new molecules able to kill Trypanosoma cruzi via an inhibition of the enzyme cruzain (also referred to as cruzipain, the full-length native enzyme).