New drug discovery strategies for the treatment of benznidazole-resistance in <i>Trypanosoma cruzi</i> , the causative agent of Chagas disease
Silvane Maria Fonseca Murta, Pedro Augusto Lemos Santana, Thibault Joseph William Jacques Dit Lapierre, André Berndt Penteado, Marissa El Hajje, Thabata Corazza Navarro Vinha, Daniel Barbosa Liarte, Mariana Laureano de Souza, Gustavo Henrique Goulart Trossini, Celso de Oliveira Rezende Júnior, Renata Barbosa de Oliveira, Rafaela Salgado Ferreira
Abstract
Introduction Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD.Areas covered Here, the authors review the current understanding of the molecular basis of benznidazole resistance. Furthermore, they discuss the state-of-the-art methods and critical outcomes employed to evaluate the efficacy of potential drugs against T. cruzi, aiming to select better compounds likely to succeed in the clinic. Finally, the authors describe the different strategies employed to overcome resistance to benznidazole and find effective new treatments for CD.Expert opinion Resistance to benznidazole is a complex phenomenon that occurs naturally among T. cruzi strains. The combination of compounds that inhibit different metabolic pathways of the parasite is an important strategy for developing a new chemotherapeutic protocol.