BIOINOVAR - Biotechnology Laboratories: Biocatalysis, Bioproducts, and Bioenergy, Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
UNIGRANRIO - Universidade do Grande Rio Programa de Pós-Graduação em Ensino das Ciências, Rio de Janeiro, Brazil.
Expert Opin Drug Discov. 2022 Oct;17(10):1147-1158. doi: 10.1080/17460441.2022.2117295. Epub 2022 Aug 29.
Carbonic anhydrase (CA) arose significant interest as a potential new target for Chagas disease since its discovery in in 2013. Benznidazole and Nifurtimox have been used for Chagas disease treatment for 60 years despite all efforts done for obtaining more efficient treatments, acting in the acute and chronic phases of illness, with fewer side effects and resistance induction.
We discuss the positive and negative aspects of CA (TcCA) studies as a target for developing new drugs. The current research discoveries and the classes of TcCA inhibitors are reviewed. The sulfonamides and their derivatives are the main inhibitor classes, but hydroxamates and the thiols, were investigated too. These compounds inhibited the growth of the evolutive forms of the parasite. A comparative analysis was done with CAs from other Trypanosomatids and protozoans.
The search for new targets and drugs is a significant challenge worldwide, and TcCA is a potential candidate for developing new drugs. Several studied inhibitors were active against , but their penetration and toxicity problems emerged. New approaches are in progress to obtain inhibitors with desired properties, allowing further steps such as tests using an adequate animal model and subsequent developments for the preclinical testing.
自 2013 年在克氏锥虫中发现碳酸酐酶(CA)以来,它作为一种潜在的新靶点引起了人们对恰加斯病的极大兴趣。尽管为获得更有效的治疗方法做出了所有努力,作用于疾病的急慢性阶段,副作用和耐药性诱导更少,但贝那唑和硝呋替莫仍被用于治疗恰加斯病已有 60 年。
我们讨论了将 CA(TcCA)作为开发新药的靶标研究的积极和消极方面。综述了当前的研究发现和 TcCA 抑制剂的类别。磺酰胺类及其衍生物是主要的抑制剂类别,但羟肟酸类和硫醇类也有研究。这些化合物抑制寄生虫进化形式的生长。与其他锥虫和原生动物的 CA 进行了比较分析。
寻找新的靶点和药物是全球面临的重大挑战,而 TcCA 是开发新药的潜在候选者。几种研究抑制剂对 有效,但它们的穿透性和毒性问题出现了。正在进行新的方法来获得具有所需特性的抑制剂,允许进一步的步骤,如使用适当的动物模型进行测试,然后进行临床前测试的开发。