Synthesis of adenine derivatives with potential antitumor and antimicrobial activity against Helicobacter pylori
Name: CLARA LIRIAN JAVARINI
Publication date: 02/03/2026
Examining board:
Name |
Role |
|---|---|
| ALVARO CUNHA NETO | Examinador Interno |
| JOSÉ ALBERTO RIBEIRO MARTINS | Examinador Externo |
| PAULA MARGARIDA VIDIGAL SOARES TEIXEIRA FERREIRA | Examinador Externo |
| PEDRO ALVES BEZERRA MORAIS | Coorientador |
| RODRIGO REZENDE KITAGAWA | Examinador Interno |
Pages
Summary: The search for new antibacterial agents is ongoing, as microbial resistance represents one of the great challenges of science. Helicobacter pylori is one of the most prevalent bacteria in the world and is recognized by the International Agency for Research on Cancer as a group I carcinogenic agent, being directly associated with the development of gastric cancer. In this context, the present work describes the synthesis of eighteen novel derivatives of adenine conjugated to peptides and dehydropeptides, which were duly characterized and evaluated for their activity against H. pylori, gastric adenocarcinoma and possible epigenetic mechanisms of action, through the inhibition of histone deacetylases (HDACs), an innovative and promising strategy in cancer treatment. The research involved in silico studies with the HDAC2 enzyme, accompanied by in vitro assays against class I/II HDACs. In this approach, compound 25 stood out for presenting more favorable interactions at the enzyme's active site, in addition to achieving the best in vitro result, with an IC value of 72.37 µM. The antitumor activity against gastric adenocarcinoma was also investigated, along with in silico studies with the Eg5 motor domain, a protein essential for the cell division process and directly related to the proliferation of cancerous cells. The results showed that compound 19d presented the highest biological activity in vitro, with an IC of 44.5 µM, followed by compound 21d, with an IC of 65.16 µM, in agreement with the data obtained in the computational analyses. Finally, the in vitro antibacterial activity against H. pylori was evaluated, associated with in silico studies with the H. pylori urease enzyme, which is fundamental for the microorganism's survival in the acidic environment of the stomach. Taken together, the results indicated that derivatives 17, 21, and 23d showed the best percentages of bacterial inhibition at a concentration of 256 µg/mL, with bacterial growth inhibition of 65.47%, 61.34%, and 60.21%, respectively. Based on these findings, it is concluded that the synthesized derivatives present a promising profile as drug candidates, with potential application in both the treatment of gastric cancer and infections associated with H. pylori.
