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Synthesis, bioactivity and mode of action of 5 A 5 B 6 C tricyclic spirolactones as novel antiviral lead compounds
Author(s) -
Zhu YuJie,
Wu QiFan,
Fan ZhiJin,
Huo JingQian,
Zhang JinLin,
Zhao Bin,
Lai Chen,
Qian XiaoLin,
Ma DeJun,
Wang DaWei
Publication year - 2019
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.5115
Subject(s) - tobacco mosaic virus , pharmacophore , moiety , tricyclic , chemistry , mode of action , lead compound , stereochemistry , in vitro , combinatorial chemistry , pharmacology , virus , biochemistry , biology , virology
Abstract BACKGROUND Plant viral diseases cause tremendous decreases in yield and quality. Natural polycyclic compounds such as those containing carbocycles are often very important lead compounds for drug and pesticide development. Tricyclic spiranoid lactones with 5 A 5 B 6 C ‐ring fusion topologies possess various bioactivities. In this study, 33 new 5 A 5 B 6 C tricyclic spirolactones were rationally designed, synthesized, characterized and evaluated for antiviral activities. RESULT These compounds showed no apparent toxicity against Italian honeybees up to 2.73 µg bee −1 . Spirolactones 14 , 16 , 19 , 23 and 28 at a concentration of 100 µg mL −1 inactivated 90% of tobacco mosaic virus (TMV) infection, making these compounds much more potent than the positive controls. Significantly, compound 19 displayed the best inactivation activity causing inhibition of up to 98%. CONCLUSION The results of the bioassays and QSAR studies indicated that the carbon‐containing cyclic moiety was the antiviral pharmacophore, and derivative 19 , which showed the best inactivation activity, could emerge as a potential antiviral agent against TMV. In vitro capsid protein (CP) assembly and TMV assembly inhibition determinations indicated that these compounds induced crosslinking in the TMV and prevented its uncoating, which was a putative new mode of action for TMV inactivation. © 2018 Society of Chemical Industry