Synthesis and antifungal activity of croconazole analogues

In order to discover compounds with better antifungal activities than croconazole hydrochloride, a series of croconazole analogues were designed and synthesized, and their antifungal activities were evaluated. By using sesamol as the starting material, 19 novel croconazole hydrochloride analogues 4a-4s were synthesized in 3 steps including acetylation, introduction of 1, 2, 4-triazole group and etherification. All the target compounds were characterized by 1H NMR, 13C NMR and ESI-MS analysis. The antifungal activities in vitro of all target compounds against seven phytopathogenic fungi (Mangnaporthe grisea, Alternaria solani, Fusarium solani, Curvulavia lunata, Alteraria alternata, Fusarium graminearum, and Fusarium oxysporum vasinfectum) were assayed, and median effective concentrations (EC50) of several compounds were further determined by mycelium growth rate inhibition method. The results demonstrated that most of target compounds exhibited significant antifungal activities against the tested strains of fungi at 50 μg/mL. Furthermore, EC50 values of compounds 4d, 4m against A. solani were 6.28 and 4.61 μg/mL, respectively; and that of 4m against A. aternata was 3.58 μg/mL. Although these data were lower than that of the positive control, myclobutanil (EC50=1.63, 1.05 μg/mL), they have been on the same order of magnitude. Thus this study demonstrated that 4d and 4m had the potential to be developed as novel antifungal drugs.