槐定碱肟醚衍生物的合成、抗菌活性及分子对接研究  

Synthesis,antibacterial activity,and molecular docking of sophorine oxime ether derivatives

作　　者：魏世洋 李金坪 伍亚晴 李清文 王立升 WEI Shiyang;LI Jinping;WU Yaqing;LI Qingwen;WANG Lisheng(School of Chemistry and Chemical Engineering,Guangxi University,Nanning 530004,China;Zhejiang Jingxin Pharmaceutical Co.,Ltd.,Xinchang 312500,China;School of Medicine,Guangxi University,Nanning 530004,China)

机构地区：[1]广西大学化学化工学院,广西南宁530004 [2]浙江京新药业股份有限公司,浙江新昌312500 [3]广西大学医学院,广西南宁530004

出　　处：《广西大学学报（自然科学版）》2023年第5期1247-1257,共11页Journal of Guangxi University（Natural Science Edition）

基　　金：广西创新驱动发展专项资金项目(桂科AA18242040)。

摘　　要：为了发现基于槐定碱的具备良好抗菌活性的化合物,设计并合成了以槐定碱为原料,在14位C上引入肟官能团并合成一系列衍生物,产率为55%~72%,所有的目标化合物通过氢核磁共振(^(1)H-NMR)、碳核磁共振(^(13)C-NMR)和电喷雾质谱法(ESI-MS)进行了表征。采用二倍稀释法检测合成的12个衍生物和槐定碱分别对2种革兰氏阴性菌细菌、2种革兰氏阳性菌以及1种真菌的抑制活性。结果表明:大部分的目标化合物相比于槐定碱的抑菌效果均有一定的提升,B_(5)和B_(12)对痤疮丙酸杆菌的抑制效果要优于阳性对照药物盐酸多西环素,其最小抑菌浓度(mininal inhibit concentration,MIC)为0.023、0.014 mg/mL。分子对接结果表明,化合物与蛋白结合形成氢键和π-π共轭作用,从而增强抑菌活性。In order to discover compounds with good antibacterial activity based on sophoridine,a series of derivatives of oxime functional groups are designed and synthesized using sophoridine as raw material and introducing oxime functional groups on 14-site C,with a yield of 55%~72%.All the target compounds are characterized by ^(1)H-NMR,^(13)C-NMR and ESI-MS.This method of modifying sophoridine structure is simple,easy post-treatment and high yield.The inhibitory activities of 12 derivatives and sophoridine against two Gram-negative bacteria,two Gram-positive bacteria and one fungus are determined by double dilution method.The results showed that most of the target compounds can improve antibacterial effect compared with sophoridine.The inhibitory effect of B_(5) and B_(12) on propionate acnes is better than that of the positive control drug doxycycline hydrochloride,with MIC values of 0.023 mg/mL and 0.014 mg/mL.The results of molecular docking shows that the compound and protein form hydrogen bond andπ-πconjugation,which enhance the antibacterial activity.

关 键 词：槐定碱 肟醚 合成 抗菌活性 分子对接 

分 类 号：O626.4[理学—有机化学]