Jun Li
The First Affiliated Hospital of Xinjiang Medical University, China
Title: Screening of kinase inhibitor library revealing lead compounds for treatment of cystic echinococcosis
Biography
Biography: Jun Li
Abstract
Abstract
Aims: The metacestode stage of two Echinococcus species, E. granulosus sensu lato and E. multilocularis cause cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. These diseases remarkably impact on the health of population. Although surgical removal of cyst is the cure treatment, about 90% of patients with echinococcal infection are treated by albendazole. However, as the drug is not parasiticidal, the patients with AE or CE have to take the drug for a long time, even for the whole life. The treatment of these diseases urgently need an effective drug.
Material and Methods: In the study, by using in vitro cultivation of E. granulosus protoscoleces and micro-cysts, we primarily screened 378 kinase inhibitors at 5 μM, which revealed 51 compounds showing killing efficacy. Further using 1 μM, 7 compounds were keeping killing efficacy in vitro. Dose-response assays revealed that 2 of the compounds, S2243 and S2895, had LC50 value below 2.5 μM. We then incubated cysts of E. granulosus collected from infected mice with S2895 and S2243 at 20 μg/L, which resulted in 60% of the cysts dead in 24 h. For in vivo efficacy trial, BALB/c mice were transferred with 50 micro-cysts and after 3 month postinfection, each of the mice was orally given these two drugs a dose of 15 mg/kg of body weight for one month. An increase in cyst mortality rate was observed compared to that of those collected from control mice.
Conclusions: Our study identifies that the two kinase inhibitors showed parasiticidal in both in vitro and in vivo, indicating these two inhibitor may be the lead-compounds for drug development against echinococcosis.