Name: NATALIA ASSIS GUEDES
Publication date: 11/11/2025
Examining board:
Name |
Role |
|---|---|
| ADILSON VIDAL COSTA | Examinador Interno |
| ALVARO CUNHA NETO | Examinador Interno |
| LUCAS DE SOUZA SOARES | Examinador Externo |
| RÓBSON RICARDO TEIXEIRA | Examinador Externo |
| VAGNER TEBALDI DE QUEIROZ | Coorientador |
Summary: In this work, triazole derivatives of nucleosides were synthesized via the CuAAC reaction (copper(I)-catalyzed alkyne-azide cycloaddition) under microwave irradiation. The structures of compounds 3a–3j were confirmed by Fourier-transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (NMR), showing characteristic signals of AZT and the triazole, with H-8 (7.76–7.83 ppm), CH3-9 (1.77– 2.06 ppm), and H-triazole (8.03–9.05 ppm) appearing as singlets, and by mass spectrometry. The compounds were obtained in yields ranging from 58.7 to 97.7%. Luminescence assays showed that compounds 3a and 3j stood out as inhibitors of SARS-CoV-2 Mpro and BCR-ABL kinase. In Mpro, 3j exhibited an IC50 of 25.15 µM and 3a of 89.18 µM, while 3e showed 168.10 µM; the other compounds did not significantly inhibit the enzyme. In BCR-ABL, 3j and 3a showed IC50 values of 0.44 µM and 0.78 µM, respectively, while 3b exhibited 150 µM and the remaining compounds were inactive. These results indicate that 3a and 3j have a promising profile as multitarget inhibitors. Molecular docking studies supported the experimental data. Compound 3a formed hydrogen bonds with key residues of Mpro, as well as hydrophobic and aromatic interactions that contribute to complex stability. In BCRABL, 3a and 3j also established hydrogen bonds and aromatic interactions. Overall, the studied triazoles demonstrated a good ability to interact with the active sites of both enzymes, suggesting potential as multi-target inhibitors. As this is an initial study, cellular assays and in vivo models are needed to confirm their biological efficacy. This work is expected to contribute to the development of new therapeutic inhibitors and to inspire future research in the field.
