Chagas disease, caused by the Trypanosoma cruzi parasite represents a major burden of public health in Latin America and a potential threat to other countries around the world. The infection is transmitted to a person via an infected triatomine bug and is in the worst, chronic form often manifested as hearth rhythm disorders and the onset of sudden cardiac failure. Despite the fact that disease was first discovered more than a century ago, only two registered medicines – benznidazole (BNZ) and nifurtimox (NF) – are available for the treatment today, where BNZ is known as the first choice medication. As nitroimidazole antiparasitic agent, it does not only give unsatisfactory results but also has numerous side effects. Treatment of Chagas disease is more than obviously a major therapeutical challenge. With the aim of discovering more effective medicines, scientists started searching for new targets as well as various modifications of already registered substances. In Brasil, where Chagas disease is most widespread, the potential active substance BZFS has been synthesized. Considering that the mechanism of action of both BNZ and BZFS is not fully explained and their effect on lipid bilayers and biological membranes has not been yet evaluated, the research of the latter was undertaken in this master's thesis. Based on the experiments and the set theoretical model, we wanted to study the course of incorporation of these substances into the phospholipid double layer, and in addition, we wanted to check whether any of them acts as a pore forming agent. For our research giant unillamelar vesicles were used. They represente a mimetic model membrane, which was prepared with using the modified method by Angelova. As basis their structure contained 1-palmitoil-2-oleoil-sn-glicero-3-fosfatidilholine (POPC) with added ergosterol or cholesterol. The selected vesicles were transferred from the stock solution compartment to the measuring cell compartment, containing solutions of BNZ or BZFS in a concentration range of 1,5 – 300 µM. Using a phase-contrast microscope, all changes in the vesicles were closely monitored and recorded with a videocamera. The measured changes were described as the final effective phases (I-XII) and quantified on the basis of the set theoretical model. Based on results we can conclude that both BNZ and BZFS interact with membrane billayer according to the described theoretical model, and none of them shows potentionally pore forming behaviour. With increasing concentrations, the effects on membranes are bigger and are also happening faster. For BNZ it can be concluded that, at the same concentrations it shows bigger incorporation into ergosterol membranes in comparison with those, containing cholesterol. On the other hand BZFS incorporates into the ergosterol and cholesterol membranes almost in the same way. At the same concentrations, BNZ is shown to have a twice higher effect on ergosterol membranes than BZFS.
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