氯康唑类似物的合成及抑菌活性

为了发现更多抑菌活性优于抗菌药物盐酸氯康唑的化合物，在盐酸氯康唑的结构基础上，设计、合成了其类似物，并进行了抑菌活性测定。以芝麻酚为原料，经过酰化、1，2，4-三氮唑基团的引入以及醚化3步反应，合成了19个新型氯康唑类似物4a~4s。所有目标化合物的结构均经过1H NMR、13C NMR和ESI-MS等确认。采用抑制菌丝生长速率法测定了目标化合物对水稻稻瘟病菌、番茄早疫病菌、马铃薯干腐病菌、玉米弯孢病菌、烟草赤星病菌、小麦赤霉病菌和棉花枯萎病菌7种植物源病原真菌的抑制活性，并进一步测定了部分化合物的EC50值。结果显示，在50 μg/mL时，大多数目标化合物对供试菌株表现出不同程度的抑制作用。其中，化合物4d和4m对番茄早疫病菌的EC50值分别为6.28和4.61 μg/mL，4m对烟草赤星病菌的EC50值3.58 μg/mL，与对照药剂腈菌唑（对番茄早疫病菌和烟草赤星病菌的EC50值分别为1.63和1.05 μg/mL）在同一数量级，具有开发为新型抗菌药物的潜能。

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 analogues4a-4s were synthesized in 3 steps including acetylation, introduction of 1, 2, 4-triazole group and etherification. All the target compounds were characterized by1H NMR,13C NMR and ESI-MS analysis. The antifungal activitiesin vitro of all target compounds against seven phytopathogenic fungi (Mangnaporthe grisea,Alternaria solani,Fusarium solani,Curvulavia lunata,Alteraria alternata, Fusarium graminearum, andFusarium 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 compounds4d,4m againstA. solani were 6.28 and 4.61 μg/mL, respectively; and that of4m againstA. 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 that4d and4m had the potential to be developed as novel antifungal drugs.