含1,2,4-三唑双席夫碱衍生物的合成、抗菌活性及分子对接

Synthesis,Antifungal Activity and Molecular Docking Study of 1,2,4-Triazole Bis-Schiff Base Derivatives

以3,5-二氨基-1,2,4-三唑与取代苯甲醛为原料成功合成了5种1,2,4-三唑双席夫碱衍生物(D1-D5)。采用菌丝生长速率法和分子对接技术研究了化合物对小麦赤霉病菌的体外抗真菌活性。结果表明,除化合物D3外,其余4种化合物的活性均优于对照药物氟康唑,其中化合物D1的抑制效果约为对照药物的1.8倍,可作为抗小麦赤霉病菌的先导化合物进一步研究。分子对接的结果与生物活性一致,即对接结合能越小,抗小麦赤霉病菌的活性越强,且氢键是维持药物分子与受体蛋白稳定结合的关键因素。为克服病原菌的耐药性问题,研究了活性最强的化合物D1和D2与氟康唑复配体系的抑菌作用,结果发现,m(D1)∶m(氟康唑)=1∶2、m(D2)∶m(氟康唑)=1∶1、1∶2、1∶4和4∶1时,共毒系数(CTC)值大于120,表现为增效作用,故化合物D2有望成为一种具有应用前景的复配用剂。

In this paper,five compounds(D1-D5)are successfully synthesized from 3,5-diamino-1,2,4-triazole and substituted benzaldehyde.The in vitro antifungal activities of the compounds against Fusarium graminearum are studied by the mycelial growth rate method and molecular docking technology.The results show that,except for compound D3,the activities of the others are superior to that of the control drug fluconazole,and the inhibitory effect of compound D1 is about 1.8 times than that of the control drug,which could be used as the lead compound against Fusarium graminearum.The results of molecular docking are consistent with the biological activity,that is,the lower the docking binding energy,the stronger the activity against Fusarium graminearum,and hydrogen bonding is the key factor to maintain the stable binding between the drug molecule and the receptor protein.In order to overcome the drug resistance of pathogenic bacteria,the antibacterial effect of the most active compounds D1 and D2 with the fluconazole combined system are investigated,and the results exhibit that co-toxicity coefficient(CTC)values are greater than 120,which shows the synergistic effect when the mass ratio of compound D1 and fluconazole is 1∶2,D2 and fluconazole is 1∶1,1∶1,1∶2,1∶4 and 4∶1,so compound D2 is expected to be a promising compound dispensing agent.