44ª Reunião Anual Virtual da SBQ

Chagas disease (CD) is classified by the UN as a neglected tropical disease, caused by the protozoan Trypanosoma cruzi and causes more than 50,000 deaths a year. There are no major investments to improve the current treatment, which are only two drugs available in the clinic since the 1940s.¹ Thus, research involving more efficient drugs for the treatment of CD is relevant to public health. In this work, we used a hybridization strategy with two classes of compounds that have been highlighted in the literature: organoselenium and 1,2,3-triazoles, to design new 1,2,3-triazole selenides and evaluate their biological potential against T. cruzi. Both have biological activities described such as antitumor, bactericidal, and antiprotozoal² and the combination of these two scaffolds appears as an alternative in the discovery of new drugs for the treatment of CD. The synthesis of the 1,2,3-triazole selenides (3a-p), was achieved by a 1,3-dipolar addition cycle with the copper and ascorbate catalytic system - as described in the scheme 1 - with aromatic azides 1 and terminal alkynes 2, previously prepared. 2,3 A series of 16 new compounds were obtained with yields ranging from 40 to 90% and confirmed by ¹H-NMR. A bioisosterism approach was applied to compound 3o, synthesized with the S atom instead of Se, to have a Structure activity relationship comparison.

The ability of these compounds in relation to the potential to inhibit cruzain, a validated target and an essential enzyme for T. cruzi,3 was investigated. In general, the compounds did not show potent activity, 0.2-28.1% (Table 1). 4 In vitro tests of antiprotozoan activity are being carried out in parallel with tests involving phenotypic activity with T. cruzi, in addition to the in silico investigation of ADME parameters, which are important for the development of new compounds with antichagasic activity. In conclusion, a series of new hybrid molecules with triazoles and chalcogenic fractions were synthesized, with investigative activity for the development of a new drug against Chagas disease.