The use of new ex vivo tests to find synthetic compounds with anthelmintic effect

Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Magdalena Mičundová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The use of new ex vivo tests to find synthetic compounds with anthelmintic effect Haemonchus contortus is a parasitic nematode causing disease called haemonchosis in sheep and goats. This worldwide spread parasite feeds on the host's bloodstream, causing anemia and edema that can lead to death of the animal. Anthelmintic drugs are used for haemonchosis treatment, but recently their efficacy has decreased due to development of drug resistance in nematodes. Therefore, it is necessary to look for new drugs that will be effective in resistant nematode strains. In this work the anthelmintic effect of 13 new benzyloxyamide derivates (BLK) was studied in H. contortus eggs and adults. An egg hatch test, in which BLK8 was the most effective compound, was used first. A new method of bioluminiscence determination of adenosine triphosphate (ATP) was used in adults of H. contortus to monitor the effect of BLK analogues on viability of adult nematodes. The efficacy of BLK analogues was compared with the effect of classical anthelmintic levamisole. It is obvious from the results that several BLK analogues (especially...