title: Design, synthesis, antiviral activity and three-dimensional quantitative structure-activity relationship study of novel 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Xiuhai
authors.initials: X
authors.lastname: Gan
authors.affiliation: 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.
authors.forename: Deyu
authors.initials: D
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: Baoan
authors.initials: B
authors.lastname: Song
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole; D003474:Curcumin
keywords: 1,3,4-oxadiazole; 1,4-pentadien-3-one; 3D-QSAR; anti-TMV; synthesis