Metabolismus nových potenciálních anthelmintik u Haemonchus contortus a u jeho hostitele
Haemonchus contortus is a parasitic nematode of small ruminants causing significant loses to many farmers worldwide. Anthelmintic drugs used for haemonchosis control are no longer effective due to drug-resistance of helminths. Therefore, there is a global need for a development of new compounds. Newly synthetized compounds BLK127 and HBK4 and already registered antipsychotic drug sertraline seem to be effective against H. contortus. However, nothing is known about their metabolism in H. contortus. Xenobiotic-metabolizing enzymes play an important role in drug resistance development and for this reason we would like to study metabolism of new potential anthelmintics in drug-resistant and drug-sensitive strains of H. contortus. Metabolites of tested compounds formed in adult worms and L3 larvae in vitro and ex vivo will be identified. In addition, we will also study metabolism and potential hepatotoxicity of these compounds in ovine liver using two model systems: primary culture of ovine hepatocytes and precision-cut liver slices. Ultra-high performance liquid chromatography-mass spectrometry technique will be used for detection and identification of metabolites. Knowledge of metabolic pathway of these drugs will provide important data for assessment of efficacy and safety of these drugs and evaluation of risk of drug resistance development.
(Full text of the project is also attached as Attachment 4)
Číslo:
GAUK1568519
Období:
01.01.2019 - 31.12.2021
Poskytovatel:
Univerzita Karlova - Grantová agentura UK
Hlavní řešitel:
Zajíčková Markéta PharmDr., Ph.D. - Farmaceutická fakulta v Hradci Králové
Celkový objem financí:
782 000,00 Kč
Interní řešitelé
Hlavní řešitel: PharmDr. Markéta Zajíčková, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Nikola Vodvárková
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: RNDr. Lucie Raisová Stuchlíková, Ph.D.
- Univerzita Karlova,
Spoluřešitel: Mgr. Pavlína Kellerová
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Mgr. Karolína Štěrbová
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Mgr. Martina Navrátilová, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Školitel: prof. RNDr. Lenka Skálová, Ph.D.
- Univerzita Karlova,