摘要/Abstract

利用生物电子等排原理和生物活性基团拼接原理, 设计合成了16个7-苯基-6H,7H-1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶类化合物. 目标化合物均经核磁共振氢谱(¹H NMR)、核磁共振碳谱(¹³C NMR)和高分辨质谱仪(HRMS)进行了结构确证. 体外抗真菌活性结果表明, 对于动物病原菌, 化合物对总状毛霉、絮状表皮癣菌、红色毛癣菌和须癣毛癣菌等浅部真菌均有较好的抑制活性, 其中化合物5d对红色毛癣菌的最小抑菌浓度为4 μg•mL ^–1, 而对新生隐球菌、白念球菌、烟曲霉等深部真菌的抑制活性较差; 化合物对5种植物病原菌均有一定程度的抑制作用, 化合物5l对花生冠腐病菌和马铃薯晚疫病菌的抑菌活性最好, 最小抑菌浓度为8 μg•mL ^–1.
关键词: 1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶, 平板法, 抗真菌活性
According to the principle of active substructure splicing and bioisosterism, sixteen 7-phenyl-6H,7H-1,3,4-thiadia- zolo[3,2-a]-thiochromeno[4,3-d]pyrimidine compounds containing a fused-ring were designed and synthesized. The target compounds were confirmed by¹H NMR, ¹³C NMR and HRMS. The preliminary antifungal activity assay showed that these compounds exhibited a good antifungal activity in vitro on superficial fungi, such as Mucor racemosus,Epidermophyton floccosum,Trichophyton rubrum and Trichophyton mentagrophytes, compound 5d was found to be very sensitive (minimum inhibitory concentration (MIC): 4 μg•mL ^–1) to Trichophyton rubrum. While on invasive fungi, such as Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus, they exhibited lower activity than that of superficial fungi. They exhibited significant inhibition activity against five plant pathogens. MIC value of compound 5l against Aspergillusnigervan tiegh and Phytophthora infestans was 8 μg•mL ^–1.
Key words: 1,3,4-thiadiazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine, plate method, antifungal activities


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