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Page 60
Volume 08
Clinical Pharmacology & Biopharmaceutics
ISSN: 2167-065X
Pharmacology 2019
World Heart Congress 2019
August 19-20, 2019
JOINT EVENT
conferenceseries
.com
August 19-20, 2019 Vienna, Austria
&
7
th
World Heart Congress
24
th
World Congress on
Pharmacology
Screening of kinase inhibitor library revealing lead compounds for treatment of cystic echinococcosis
Jun Li, Tian Wang, WenJing QI, Li He and WenBao Zhang*
The First Affiliated Hospital of Xinjiang Medical University, China
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.
Recent Publications:
1.
Jianling Bao,Jun Li(2018) Donald McManus. Echinococcus granulosus infection results in an increase in
Eisenbergiella and Parabacteroides genera in the gut of mice, Frontiers in Microbiology.29 November 2018.
2.
Hui Wang, Jun Li (2018) Echinococcus granulosus sensu stricto: silencing of thioredoxin 4 peroxidase impairs
the differentiation of protoscoleces into 5 metacestodes. Parasite 25, 57.
3.
Zhuang-Zhi Zhang,Wen-Bao Zhang(2018)Dog vaccination with EgM proteins against Echinococcus
granulosus.[J]. Infectious Diseases of Poverty,7(1):61.
4.
Mei Yang, Wenbao Zhang(2017)Cloning and characterization of an Echinococcus granulosus ecdysteroid
hormone nuclear receptor HR3-like gene.[J]. Parasite-journal De La Societe Francaise De Parasitologie, 24:36
5.
Weisi Wang, Jun Li(2017)In vitro and in vivo efficacies of novel carbazole aminoalcohols in the treatment of
cystic echinococcosis. J Antimicrob Chemother. Jul 24. doi: 10.1093/jac/dkx250.
6.
Wu C, Li J(2017)Genetic variation of mitochondrial genes among Echinococcus multilocularis isolates
collected in western China. Parasit Vectors. May 30;10(1):265. doi: 10.1186/s13071-017-2172-y.
7.
Wang H, Li J (2016) In vitro culture of Echinococcus multilocularis producing protoscoleces and mouse
infection with the cultured vesicles. Parasites & Vectors.Jul 25;9(1):411
Biography
Jun Li is a professor of Xinjiang Medical University and a senior research fellow of State Key Laboratory of Pathogenesis, Prevention and Treatment of High
Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China. He received her B. Sc from Xinjiang Medical University. In 2004, she obtained
her PhD at the University of Queensland working on developing diagnosis tool for detecting cystic echinococcosis. She then spent 3 years working on PanBio
for developing diagnosis kit for infectious diseases. From 2008-2013, she worked on molecular biology of Echinococcus as a senior research officer in Molecular
Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. She has published more than 30
papers/articles in the international journals in her research career.
Jun Li et al., Clin Pharmacol Biopharm, Volume 08