Sleeping sickness and leishmaniasis are neglected tropical
diseases
that threaten millions of people. The currently available therapies
present several limitations, including high toxicity, lack of efficacy,
and emerging drug resistance, prompting a search for novel therapeutic
agents. In this work, we designed, synthesized, and in vitro evaluated the activity of new pyrimido[5,4-d]pyrimidines
against Trypanosoma brucei and Leishmania
infantum (promastigote and amastigote forms). The cytotoxicity
of the compounds against the THP1 cell line was also assessed. Most
tested compounds presented low micromolar activity against T. brucei with IC50 values in the range between
0.9 and 13.4 μM, and one compound also showed activity against L. infantum (IC50 = 3.13 μM). Several molecules
presented a selectivity index higher than 10. The most active compound
against booth parasites is derivative 4c, with IC50 = 0.94 μM (SI > 107) against T. brucei and IC50 = 3.13 μM (SI > 32) against L.
infantum. This data enabled the identification of a new promising
molecular scaffold for developing a novel class of antitrypanosomal
and antileishmanial agents.
The present work focused on the development of a fluorescence resonance energy transfer (FRET)-based sensing platform for the monitoring of atenolol in pharmaceutical formulations. The implemented approach involved the assembly...
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