In agriculture, the control of fungal infections is essential to improve crop quality and productivity. This study describes the preparation and fungicidal activity evaluation of 12 glycerol derivatives bearing 1,2,3-triazole fragments. The derivatives were prepared from glycerol in four steps. The key step corresponded to the Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction between the azide 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes (57-91% yield). The compounds were characterized by infrared spectroscopy, nuclear magnetic resonance (1H and 13C), and high-resolution mass spectrometry. The in vitro assessment of the compounds on Asperisporium caricae, that is, the etiological agent of papaya black spot, at 750 mg L-1 showed that the glycerol derivatives significantly inhibited conidial germination with different degrees of efficacy. The most active compound 4-(3-chlorophenyl)-1-((2,2-dimethyl-1,3-dioxolan-4-yl) methyl)-1H-1,2,3-triazole (4c) presented a 91.92% inhibition. In vivo assays revealed that 4c reduced the final severity (70.7%) and area under the disease severity progress curve of black spots on papaya fruits 10 days after inoculation. The glycerol-bearing 1,2,3-triazole derivatives also present agrochemical-likeness properties. Our in silico study using molecular docking calculations show that all triazole derivatives bind favorably to the sterol 14α-demethylase (CYP51) active site at the same region of the substrate lanosterol (LAN) and fungicide propiconazole (PRO). Thus, the mechanism of action of the compounds 4a-4l may be the same as the fungicide PRO, blocking the entrance/approximation of the LAN into the CYP51 active site by steric effects. The reported results point to the fact that the glycerol derivatives may represent a scaffold to be explored for the development of new chemical agents to control papaya black spot.
Keywords: 1,2,3-triazole; Asperisporium caricae; black spot; glycerol; molecular docking; papaya.