Rejuvenating the [1, 2, 3]-triazolo [1,5-a]quinoxalin-4(5 H )-one scaffold: Synthesis and derivatization in a sustainable guise and preliminary antimicrobial evaluation

• Published in: Frontiers in chemistry 2023-03, Vol.11, p.1126427-1126427
• Main Authors: Pelliccia, Sveva, Alfano, Antonella Ilenia, Gomes Da Assunção, Beatriz Ramos, Turco, Luigia, Lembo, Francesca, Summa, Vincenzo, Buommino, Elisabetta, Brindisi, Margherita
• Format: Article
• Language: English
• Subjects: [1,2,3]-triazolo [1,5-a] quinoxalin-4(5H)-one; antimicrobial agents; Chemistry; drug discovery; green chemistry; privileged scaffold; sustainable synthesis
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2023.1126427

The [1,2,3]-triazolo [1,5-a] quinoxalin-4(5 )-one scaffold and its analogues triazole-fused heterocyclic compounds are relevant structural templates in both natural and synthetic biologically active compounds. However, their medicinal chemistry applications are often limited due to the lack of synthetic protocols combining straightforward generation of the central core while also allowing extensive decoration activity for drug discovery purposes. Herein, we report a "refreshed" synthesis of the [1,2,3]-triazolo [1,5- ]quinoxalin-4(5 )-one core, encompassing the use of eco-compatible catalysts and reaction conditions. We have also performed a sustainable and extensive derivatization campaign at both the endocyclic amide nitrogen and the ester functionality, comprehensively exploring the reaction scope and overcoming some of the previously reported difficulties in introducing functional groups on this structural template. Finally, we unveiled a preliminary biological investigation for the newly generated chemical entities. Our assessment of the compounds on different bacterial species (two strains, three strains, ), and two fungal strains, as well as the evaluation of their activity on biofilm formation, foster further optimization for the retrieved hit compounds , , and .