摘要/Abstract

为寻找高效农用抗菌先导化合物, 通过活性亚结构拼接法设计合成了50个含6-氟喹唑啉片段的新型1,3,4-噁(噻)二唑类衍生物6a~6y和8a~8y, 其结构经¹H NMR、¹³C NMR和HRMS手段进行了表征, 且化合物6i和8x的结构最终由X射线单晶衍射法加以确认. 初步抗菌测试表明, 部分化合物表现出较好的体外抗真菌活性. 在50 μg/mL浓度下, 化合物 6b、6d、6t、6v和6x对小麦赤霉病菌的抑制率分别为58%、58%、55%、63%和60%, 化合物6v和8v对苹果腐烂病菌的抑制率分别为71%和64%, 化合物6v对油菜炭疽病菌的抑制率为72%, 它们均优于对照药剂噁霉灵(分别为51%、61%和70%). 此外, 部分化合物在100 μg/mL浓度下也表现出一定的体外抗细菌活性.
关键词: 1,3,4-噁二唑, 1,3,4-噻二唑, 6-氟喹唑啉, 合成, 抗菌活性
To search efficient agricultural antimicrobial lead compounds, fifty 1,3,4-oxa(thia)diazole derivatives 6a~6y and 8a~8y containing 6-fluoroquinazoline moiety were designed, synthesized and evaluated for their antimicrobial activities, based on the method of the splicing of bioactive substructures. The structures of target compounds were fully characterized by ¹H NMR, ¹³C NMR, and HRMS spectra, and two compounds 6i and 8x were further confirmed via single crystal X-ray diffraction analysis. The preliminary bioassays revealed that some compounds exhibited good antifungal activity in vitro. For example, compounds 6b, 6d, 6t, 6v and 6x were found to have the inhibition rates of 58%, 58%, 55%, 63% and 60% against Gibberella zeae at 50 μg/mL, respectively. Additionally, compounds 6v and 8v displayed the inhibition efficacies of 71% and 64% against Cytospora mandshurica at 50 μg/mL, respectively. Moreover, compound 6v demonstrated an inhibition rate of 72% against Colletotrichum gloeosporioides at 50 μg/mL. The above activities were all better than that of control agent Hymexazol (51%, 61%, and 70%, respectively). Finally, some compounds also showed certain inhibition potencies in vitro against tested bacteria at 100 μg/mL.
Key words: 1,3,4-oxadiazole, 1,3,4-thiadiazole, 6-fluoroquinazoline, synthesis, antimicrobial activity


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