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

• Published in: Pest management science 2016-03, Vol.72 (3), p.534-543
• Main Authors: Gan, Xiuhai, Hu, Deyu, Li, Pei, Wu, Jian, Chen, Xuewen, Xue, Wei, Song, Baoan
• Format: Article
• Language: English
• Subjects: 1,3,4‐oxadiazole; 1,4‐pentadien‐3‐one; 3D-QSAR; 4-oxadiazole; 4-pentadien-3-one; anti-TMV; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Curcumin - analogs & derivatives; Curcumin - chemical synthesis; Curcumin - pharmacology; Drug Design; Microbial Sensitivity Tests; Molecular Conformation; Oxadiazoles - chemical synthesis; Oxadiazoles - pharmacology; Quantitative Structure-Activity Relationship; synthesis; Tobacco mosaic virus; Tobacco Mosaic Virus - drug effects
• ISSN: 1526-498X; 1526-4998
• DOI: 10.1002/ps.4018

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 q² and r² 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. 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