Gan Xiuhai, Hu Deyu, Li Pei, Wu Jian, Chen Xuewen, Xue Wei, Song Baoan
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Centre for Research and Development of Fine Chemicals, Guizhou University, Guiyang, China.
College of Chemistry and Life Science, Guizhou Normal College, Guiyang, China.
Pest Manag Sci. 2016 Mar;72(3):534-43. doi: 10.1002/ps.4018. Epub 2015 May 8.
1,4-Pentadien-3-one and 1,3,4-oxadiazole derivatives possess good antiviral activities, and their substructure units are usually used in antiviral agent design. In order to discover novel molecules with high antiviral activities, a series of 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety were designed and synthesised.
Bioassays showed that most of the title compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV) in vivo. The compound 8f possessing the best protective activity against TMV had an EC50 value of 135.56 mg L(-1) , which was superior to that of ribavirin (435.99 mg L(-1) ). Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were used in three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of protective activities, with values of q(2) and r(2) for the CoMFA and CoMSIA models of 0.751 and 0.775 and 0.936 and 0.925 respectively. Compound 8k with higher protective activity (EC50 = 123.53 mg L(-1) ) according to bioassay was designed and synthesised on the basis of the 3D-QSAR models.
Some of the title compounds displayed good antiviral activities. 3D-QSAR models revealed that the appropriate compact electron-withdrawing and hydrophobic group at the benzene ring could enhance antiviral activity. These results could provide important structural insights for the design of highly active 1,4-pentadien-3-one derivatives.
1,4-戊二烯-3-酮和1,3,4-恶二唑衍生物具有良好的抗病毒活性，其亚结构单元常用于抗病毒药物设计。为发现具有高抗病毒活性的新型分子，设计并合成了一系列含1,3,4-恶二唑部分的1,4-戊二烯-3-酮衍生物。
生物活性测定表明，大多数目标化合物在体内对烟草花叶病毒（TMV）表现出良好的抑制活性。对TMV具有最佳保护活性的化合物8f的EC50值为135.56 mg L(-1)，优于利巴韦林（435.99 mg L(-1)）。采用比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）技术对保护活性进行三维定量构效关系（3D-QSAR）研究，CoMFA和CoMSIA模型的q(2)和r(2)值分别为0.751和0.775以及0.936和0.925。根据生物活性测定，基于3D-QSAR模型设计并合成了具有较高保护活性（EC50 = 123.53 mg L(-1)）的化合物8k。
部分目标化合物显示出良好的抗病毒活性。3D-QSAR模型表明，苯环上适当的紧凑吸电子和疏水基团可增强抗病毒活性。这些结果可为高活性1,4-戊二烯-3-酮衍生物的设计提供重要的结构见解。
