Novel and Selective Triosephosphate Isomerase Inhibitors with Acaricidal Activity.

The cattle tick 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 to most of these products, some even to more than one active principle. Thus, exploration for new molecules with acaricidal activity in has become necessary. Triosephosphate isomerase (TIM) is an essential enzyme in 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 . Four compounds (, , , and ) selectively inhibited this enzyme with IC values between 25 and 50 μM. They were also able to diminish cellular viability of BME26 embryonic cells by more than 50% at 50 μM. A molecular docking study showed that the compounds bind in different regions of the protein; compound interacts with the dimer interface. Furthermore, compound 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 as a prototype for development of a new acaricidal involving selective TIM inhibition.