1,2,3-Triazole Hybrids Containing Isatins and Phenolic Moieties: Regioselective Synthesis and Molecular Docking Studies

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-04, Vol.29 (7), p.1556
• Main Authors: Maiuolo, Loredana, Tallarida, Matteo Antonio, Meduri, Angelo, Fiorani, Giulia, Jiritano, Antonio, De Nino, Antonio, Algieri, Vincenzo, Costanzo, Paola
• Format: Article
• Language: English
• Subjects: Acids; Alkynes; Antifungal agents; Antioxidants; Azide; Cancer; CuAAC; Drug discovery; Enzymes; Isatin; isatin hybrids; Molecular Docking Simulation; Phenols; Solvents; Temperature; triazole hybrids; Triazoles
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29071556

The synthesis of hybrid molecules is one of the current strategies of drug discovery for the development of new lead compounds. The 1,2,3-triazole moiety represents an important building block in Medicinal Chemistry, extensively present in recent years. In this paper, we presented the design and the synthesis of new 1,2,3-triazole hybrids, containing both an isatine and a phenolic core. Firstly, the non-commercial azide and the alkyne synthons were prepared by different isatines and phenolic acids, respectively. Then, the highly regioselective synthesis of 1,4-disubstituted triazoles was obtained in excellent yields by a click chemistry approach, catalyzed by Cu(I). Finally, a molecular docking study was performed on the hybrid library, finding four different therapeutic targets. Among them, the most promising results were obtained on 5-lipoxygenase, an enzyme involved in the inflammatory processes.