含喹唑啉酮的查尔酮衍生物的设计、合成及生物活性研究  

Design, Synthesis and Bioactivity of Chalcone Derivative Containing Quinazolinone

作　　者：周然 袁春梅 张桃 毛飘 刘燚 孟开妮 幸惠 薛伟[1] Zhou Ran;Yuan Chunmei;Zhang Tao;Mao Piao;Liu Yi;Meng Kaini;Xin Hui;Xue Wei(National Key Laboratory of Green Pesticide,Key Laboratory of Green Pesticide and Agricultural Bioengineering,Ministry of Education,Guizhou University,Guiyang 550025)

机构地区：[1]贵州大学绿色农药全国重点实验室、绿色农药与生物工程教育部重点实验室,贵阳550025

出　　处：《有机化学》2023年第9期3196-3209,共14页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(32072446);贵州省科学基金(20192452)。

摘　　要：设计合成了25个含喹唑啉酮的查尔酮衍生物.抗病毒生物实验结果表明,(E)-3-(4-氯苯基)-6-氟-2-((2-(4-(3-(4-甲氧基苯基)丙烯酰基)苯氧基)乙基)硫代)喹唑啉-4(3H)-酮(Z12)对烟草花叶病毒(tobacco mosaic virus,TMV)有较好的抑制活性,治疗和保护的EC_(50)值分别为94.3和98.8μg/mL,优于对照药宁南霉素(ningnanmycin,NNM)的216.1和189.6μg/mL.透射电镜结果表明,Z12使得TMV病毒颗粒断裂,形成长短不一的棒状结构,微量热涌动实验(MST)的结果表明,Z12对烟草花叶病毒外壳蛋白(TMV-CP)结合的Kd值为(0.033±0.014)μmol/L,优于宁南霉素的Kd值[(0.106±0.024)μmol/L],说明了Z12对TMV-CP具有更强的结合力.抑菌实验结果表明,部分化合物对水稻白叶枯病菌(Xanthomonas oryzae pv.Oryzae,Xoo)和柑桔溃疡病菌(Xanthomonas axonopodis pv.Citri,Xac)表现出优异活性,其中(E)-2-((2-(4-(3-(4-溴苯基)丙烯酰基)苯氧基)乙基)硫代)-3-(4-氯苯基)-6-硝基喹唑啉-4(3H)-酮(Z25)对Xoo活性最好,EC_(50)值为19.5μg/mL,优于叶枯唑(77.1μg/mL)和噻菌铜(95.9μg/mL).扫描电镜结果表明,Z25作用后使得Xoo的细胞膜皱缩变形.上述实验结果表明含喹唑啉酮的查尔酮衍生物是有潜力的抗病毒和抑菌药物.Twenty-five chalcone derivatives containing quinazolinone were designed and synthesized. The results of antiviral biological experiments showed that (E)-3-(4-chlorophenyl)-6-fluoro-2-((2-(4-(3-(4-methoxyphenyl)acryloyl)phenoxy)ethyl)- thio)quinazolin-4(3H)-one (Z12) had a good inhibitory activity against tobacco mosaic virus (TMV), and the EC_(50) values of treatment and protection were 94.3 and 98.8 μg/mL, respectively, which were better than those of ningamycin (NNM, 216.1 and 189.6 μg/mL). The results of transmission electron microscope showed that Z12 broke TMV virus particles and formed rod structures of different lengths. The results of microscale thermophoresis experiment (MST) showed that the Kd value of Z12 binding to tobacco mosaic virus coat protein (TMV-CP) was (0.033±0.014) μmol/L. The Kd value of Z12 was better than that of ningnanmycin [(0.106±0.024) μmol/L], which indicated that Z12 had stronger binding ability to TMV-CP. The antibacterial test results showed that some compounds showed excellent activity against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv.Citri (Xac), among which ((E)-2-((2-(4-(3-(4-bromophenyl)acryloyl)phenoxy)ethyl)thio)-3- (4-chlorophenyl)-6-nitroquinazolin-4(3H)-one (Z25) showed the best activity against Xoo. The EC_(50) value of Xoo was 19.5 μg/mL, which was better than those of bismerthiazol (77.1 μg/mL) and thiodiazole copper (95.9 μg/mL). The results of scanning electron microscope showed that the cell membrane of Xoo was shriveled and deformed after Z25 treatment. The experimental results showed that chalcone derivatives containing quinazolinone were potential antiviral and antibacterial drugs.

关 键 词：喹唑啉酮 查尔酮 有机合成 抑菌 抗病毒 

分 类 号：O626[理学—有机化学] TQ460.1[理学—化学]