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ChemMedChem ; 16(23): 3600-3614, 2021 12 06.
Article in English | MEDLINE | ID: mdl-34665510

ABSTRACT

Leishmaniasis and Chagas diseases are two of the most important parasitic diseases in the world. Both belong to the category of Neglected Tropical Diseases, and they cannot be prevented by vaccination. Their treatments are founded in outdated drugs that possess many pernicious side-effects and they're not easy to administer. With the aim of discovering new compounds that could serve as anti-trypanosomal drugs, an antiparasitic study of a synthetic compound family has been conducted. A series of new 1,4-bis(alkylamino)- and 1-alkylamino-4-chloroazine and benzoazine derivatives 1-4 containing imidazole rings have been synthesized and identified. Their structures showed a possible interest based on previous work. Their in vitro anti-Leishmania infantum, anti-L. braziliensis, anti-L. donovani and anti-T. cruzi activity were tested, as well as the inhibition of Fe-SOD enzymes. It was found that some of them exhibited quite relevant values indicative of being worthy of future more detailed studies, as most of them showed activity to more than only one parasite species, especially compound 3 c was active for the three studied Leishmania species and also for T. cruzi, which is a very interesting trait as it covers a wide spectrum.


Subject(s)
Imidazoles/pharmacology , Phthalazines/pharmacology , Pyridazines/pharmacology , Trypanocidal Agents/pharmacology , Animals , Chlorocebus aethiops , Imidazoles/chemical synthesis , Imidazoles/toxicity , Leishmania braziliensis/drug effects , Leishmania donovani/drug effects , Leishmania infantum/drug effects , Parasitic Sensitivity Tests , Phthalazines/chemical synthesis , Phthalazines/toxicity , Pyridazines/chemical synthesis , Pyridazines/toxicity , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/toxicity , Trypanosoma cruzi/drug effects , Vero Cells
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