Synthesis, crystal structure, in vitro antifungal activity and molecular docking of 3-(1-((4H-1,2,4-triazol-4-yl)imino) ethyl)-2H-benzopyran-2-one derivatives

Thirteen novel 3-(1-((4H-1,2,4-triazol-4-yl)imino)ethyl)-2H-benzopyran-2-one derivatives (TEMC-1-TEMC-13) were synthesized. The structure of compounds were verified by NMR, IR and HRMS. The crystal structures of TEMC-6 and TEMC-12 were determined by single-crystal X-ray diffraction (XRD), they are monoclinic systems P21/c space group and triclinic systems, respectively P-1 space group and the crystal structure showed the presence of intermolecular and intramolecular hydrogen bonds played an important role in the activity effect. The in vitro antifungal activity results of the synthesized compounds against Fusarium graminearum showed that methyl and alkoxy-substituted compounds had good biological activity. Among of them, TEMC-7 had the best effect (EC50 = 6.74 mu g/mL) than that of others and the commercial drug fluconazole (EC50=10.19 mu g/mL) with the lasting antifungal effect. Molecular docking was used to predict the binding mode of ligands with CYP51. The active sites with good active compounds included coumarin groups and residues TRY A:105, triazole groups and residues ALA A:291, as well as methyl on Schiff base structure and receptor center HEM A:601, achieving at least three different ways of action.