Acaricidal activity of strophanthidin derivatives against Psoroptes cuniculi and their inhibitory effect on Na+-K+-ATPase

In our previous studies, we found that as the active gradients of Adonis coerulea, cardenolides and cardiac glycosides presented toxicity against mites by inhibiting Na+-K+-ATPase. In this paper, after evaluating the acaricidal activity of the commercial cardiac aglycones/glycosides, serials of novel strophanthidin derivatives were designed and synthesized with an efficient and simple route under mild conditions, and their toxicity against mites, the cytotoxicity and inhibitory effect on Na+-K+-ATP enzyme in PC12 cells were investigated. Results showed among of all compounds, including 9 commercial agent and 32 synthesized strophanthidin derivatives, QXG-1 presented the strongest toxicity against mites with the LC(50 )value of 320.0 mu g/mL. C-19 group of strophanthidin substituted with glycinemethylester would increase the toxicity against mites, and the hydroxyl group at C-5 play the vital role in terms of the toxicity. At the given concentration, QXG-1 displayed the safety against PC12 (10.0 mu g/mL) in vitro and mice (3.2 mg/kg) in acute toxicity test, and strong inhibitory effect on Na+-K+-ATPase. It could be used as a promising acaricidal agent. This study lays the foundation to develop of QXG-1 as a relatively safe and alternative acaricidal agent.

Automated summary

This study confirmed the strong acaricidal activity and inhibitory effect on Na+-K+-ATPase of the novel strophanthidin derivative QXG-1. By chemically modifying specific positions of the strophanthidin molecule, its toxicity against mites can be controlled. The safety of QXG-1 in vitro and in vivo also suggests its potential as a promising acaricidal agent.