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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
Author(s) -
Gan Xiuhai,
Hu Deyu,
Li Pei,
Wu Jian,
Chen Xuewen,
Xue Wei,
Song Baoan
Publication year - 2016
Publication title -
pest management science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.296
H-Index - 125
eISSN - 1526-4998
pISSN - 1526-498X
DOI - 10.1002/ps.4018
Subject(s) - moiety , quantitative structure–activity relationship , oxadiazole , chemistry , stereochemistry , ec50 , lead compound , tobacco mosaic virus , bioassay , structure–activity relationship , combinatorial chemistry , in vitro , virus , biology , organic chemistry , biochemistry , virology , genetics
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 EC 50 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 ( EC 50 = 123.53 mg L −1 ) according to bioassay was designed and synthesised on the basis of the 3D‐QSAR models. CONCLUSION 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. © 2015 Society of Chemical Industry