Synthesis and Biological Evaluation of Cytotoxic Paeonol Derivatives, Aryne-Functionalized Naphthoquinones with Trypanocidal Activity, and BODIPY-Based Fluorophores
Name: LAURA PATRICIA ROCHA FIGUEROA
Publication date: 11/12/2025
Examining board:
Name |
Role |
|---|---|
| ALVARO CUNHA NETO | Examinador Interno |
| AMANDA SILVA DE MIRANDA | Examinador Externo |
| EUFRANIO DA SILVA JUNIOR | Coorientador |
| JULIANA CHRISTINA THOMAS | Examinador Externo |
| LUIS OCTAVIO REGASINI | Examinador Externo |
Pages
Summary: This work presents three projects related to the organic synthesis of natural product derivatives and bioluminescent moieties with different applications. The first project focused on Paeonol-related compounds and their biological potential through the synthesis of Paeonol-derived ethers and benzofurans via bimolecular nucleophilic substitution reactions. A total of four ether derivatives and seven benzofuran derivatives were obtained. The cytotoxic activity of all synthesized compounds was evaluated, and three compounds were active against the HCT116 cell line, showing over 60% growth inhibition. Notably, compound 44e exhibited a strong IC50 value of 0.2 M, supporting its potential as an anticancer agent. The second study explored the regioselective synthesis of functionalized 1,4-naphthoquinones via aryne chemistry, through the generation and trapping of naphthoquinonynes. Twelve amine derivatives and six pyridine N-oxide derivatives were obtained, providing access to A-ring functionalized naphthoquinones, including nine new compounds. Their trypanocidal activity was evaluated, and fourteen naphthoquinones showed higher activity than benznidazole, the current drug used for Chagas disease. Two compounds were approximately ten times more potent. These results highlight the value of this approach for the discovery of new trypanocidal agents and demonstrate the efficiency and versatility of the methodology. The third chapter showed the design and synthesis of BODIPY-based fluorescent molecules. A series of krypto-BODIPY and meso-phenyl BODIPY derivatives was synthesized, including eight new compounds such as mono- and di-halogenated scaffolds, acetylated analogues, Sonogashira coupling products, and a symmetric bis-BODIPY alkyne. The results demonstrate that both kryptopyrrole and meso-phenyl frameworks tolerate electrophilic substitution, C–H activation, and Pd-catalyzed cross-coupling reactions, enabling efficient diversification of BODIPY fluorophores. Overall, this work demonstrates the development of efficient synthetic strategies for biologically relevant and fluorescent molecular scaffolds, contributing new compounds and methodologies with potential applications in medicinal chemistry and chemical biology.
