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
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引用次数: 0
摘要
导言:苯并咪唑是治疗南美锥虫病(CD)的首选药物,但它有很大的局限性,如疗效不佳(主要是在 CD 的慢性期)、副作用和寄生虫抗药性。了解寄生虫对苯并咪唑的抗药性对于开发治疗南美锥虫病的新药至关重要:在此,作者回顾了目前对苯并咪唑耐药性分子基础的理解。此外,他们还讨论了评估潜在药物对 T. cruzi 的疗效所采用的最先进方法和关键结果,旨在筛选出可能在临床上取得成功的更好的化合物。最后,作者介绍了为克服苯并咪唑耐药性并找到有效的CD新疗法而采用的不同策略:对苯并咪唑的耐药性是一种复杂的现象,在克鲁斯绦虫菌株中自然存在。结合抑制寄生虫不同代谢途径的化合物是开发新化疗方案的重要策略。
New drug discovery strategies for the treatment of benznidazole-resistance in Trypanosoma cruzi, the causative agent of Chagas disease.
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.
期刊介绍:
Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
The Editors welcome:
Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology
Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug
The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.