Novel and selective Rhipicephalus microplus triosephosphate isomerase inhibitors with acaricidal activity

• Autor(a) principal: Saramago, Luiz
• Data de Publicação: 2018
• Outros Autores: Gomes, Helga, Aguilera, Elena, Cerecetto, Hugo, González, Mercedes, Cabrera, Mauricio, Alzugaray, Maria Fernanda, Vaz Junior, Itabajara da Silva, Fonseca, Rodrigo N. da, Aguirre-López, Beatriz, Cabrera, Nallely, Pérez-Montfort, Ruy, Merlino, Alicia, Moraes, Jorge, Álvarez, Gusmán
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/182479
• topic: Inibidores enzimaticos; Triose-fosfato isomerase; Acaricida; Rhipicephalus microplus; Carrapato bovino; Triosephosphate isomerase inhibitors; Rhipicephalus microplus; Acaricidal compounds

The cattle tick Rhipicephalus microplus is one of the most important ectoparasites causing significant economic losses for the cattle industry. The major tool of control is reducing the number of ticks, applying acaricides in cattle. However, overuse has led to selection of resistant populations of R. microplus to most of these products, some even to more than one active principle. Thus, exploration for new molecules with acaricidal activity in R. microplus has become necessary. Triosephosphate isomerase (TIM) is an essential enzyme in R. microplus metabolism and could be an interesting target for the development of new methods for tick control. In this work, we screened 227 compounds, from our in-house chemo-library, against TIM from R. microplus. Four compounds (50, 98, 14, and 161) selectively inhibited this enzyme with IC50 values between 25 and 50 M. They were also able to diminish cellular viability of BME26 embryonic cells by more than 50% at 50 M. A molecular docking study showed that the compounds bind in different regions of the protein; compound 14 interacts with the dimer interface. Furthermore, compound 14 affected the survival of partially engorged females, fed artificially, using the capillary technique. This molecule is simple, easy to produce, and important biological data—including toxicological information—are available for it. Our results imply a promising role for compound 14 as a prototype for development of a new acaricidal involving selective TIM inhibition.