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The linker length of glucose–fipronil conjugates has a major effect on the rate of bioactivation by β‐glucosidase
Author(s) -
Wen Yingjie,
Jiang Xunyuan,
Yang Chen,
Meng Huayue,
Wang Binfeng,
Wu Hanxiang,
Zhang Zhixiang,
Xu Hanhong
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.5170
Subject(s) - fipronil , chemistry , trifluoromethyl , hydrolysis , stereochemistry , docking (animal) , biochemistry , organic chemistry , pesticide , biology , medicine , alkyl , nursing , agronomy
Abstract BACKGROUND Endogenous plant β‐glucosidases can be utilized to hydrolyze pro‐pesticides and release the bioactive pesticide. Two related glucose–fipronil conjugates with different linkers structure, N ‐{3‐cyano‐1‐[2,6‐dichloro‐4‐(trifluoromethyl) phenyl]‐4‐[(trifluoromethyl) sulfinyl]‐1 H ‐pyrazol‐5‐yl}‐1‐(2‐triazolethyl‐ β ‐ d ‐glucopyranoside)‐1 H ‐1,2,3‐triazole‐4‐methanamine (GOTF) and N ‐{3‐cyano‐1‐[2,6‐dichloro‐4‐(trifluoromethyl) phenyl]‐4‐[(trifluoromethyl)‐sulfinyl]‐1 H ‐pyrazol‐5‐yl}‐2‐aminoethyl‐ β ‐ d ‐glucopyranoside (GOF), were deglucolysated by β‐glucosidase both in vitro and in vivo at different rates. Here, the basis for these differences was investigated by revealing the kinetics of the reaction and by modeling molecular docking between enzyme and substrate. RESULTS Results from kinetic study showed that the reaction rate was the main reason for the poorer rate of GOF hydrolysis with respect to GOTF. Modeling of substrate docking indicated that the spacer arm of glucose–fipronil conjugates affects the strength of non‐covalent bonds within the active site and the position of fipronil within the pocket. Four glucose–fipronil conjugates and four corresponding aglycones were synthesized, and the hydrolysis data confirmed that the increased tether length between the bulky aglycone and glycone would lead to faster hydrolysis rate. The bioassay results indicated that most glucose–fipronil conjugates displayed moderate to excellent insecticidal activities in vivo against Plutella xylostella larvae. CONCLUSION This study provides a potential strategy to optimize the substrate structure to enhance hydrolytic specificity in order to design appropriate phloem mobile pro‐pesticides. © 2018 Society of Chemical Industry