American trypanosomiasis also known as Chagas disease is a disease caused by the protozoan parasite Trypanosoma cruzi. It represents a major public health burden in Latin America and due to large-scale population movements in recent years, a potential threat to a number of countries throughout the world at the same time. The lack of public policies and the disinterest from pharmaceutical industries in the development of new drugs for neglected tropical diseases, leaving only two registered medicines for the treatment of Chagas disease – benznidazole and nifurtimox. Both compounds are effective in the acute phase, but their usefulness in chronic stage has a low clinical efficacy due to a narrow therapeutic window, strong side effects and variable sensitivities among T. cruzi strains.
In the search of effective drugs, many studies and efforts have been made, but only a few structures have emerged as suitable candidates. From the structure–activity relationship’s viewpoint, there is still no clarity on the major factors expressing antiparasitic properties, but researches reinforce the importance of the electrophilic character of the molecule and the N-oxide moiety, which is thought to be responsible for the trypanocidal activity of the compound, since it can cause oxidative stress in the parasite. In particular, they are developing such new substances, and they are also trying to modulate some specific targets in the parasite.
According to the available literature, we have found that benzofuroxane derivatives have already shown excellent in vitro and in vivo results, semi- and thiosemicarbazones have also proven to be an interesting class of ligands. In our thesis, we decided to synthesize semi- and thiosemicarbazide derivatives. Ten compounds were successfully synthesized, two of which in the side chain contained benzofuroxane, others benzene with substituents (-NO2, -Cl) at different sites in the ring. Most reactions were single-stage and easy to synthesize, their yields were satisfactory (above 72 %). The purification of products was difficult because of their poor solubility, which also applies to the output semi- and thiosemicarbazide.
The compounds were tested for their trypanocidal activity on the epimastigotic form of T. cruzi (Y strain). Given the IC50 value of the therapeutically useful benznidazole, the compounds 3 and 6 have been shown to be trypanocidal active agents.
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