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Download fileSynthesis, Optimization, and Evaluation of Glycosylated Naphthalimide Derivatives as Efficient and Selective Insect β‑N‑Acetylhexosaminidase OfHex1 Inhibitors
journal contribution
posted on 2019-05-15, 00:00 authored by Shengqiang Shen, Lili Dong, Wei Chen, Renjie Wu, Huizhe Lu, Qing Yang, Jianjun ZhangInsect chitinolytic β-N-acetylhexosaminidase
OfHex1, from the agricultural pest Ostrinia furnacalis (Guenée), is considered as a potential target for green pesticide
design. In this study, rational molecular design and optimization
led to the synthesis of compounds 15r (Ki = 5.3 μM) and 15y (Ki = 2.7 μM) that had superior activity against OfHex1
than previously reported lead compounds. Both compounds 15r and 15y had high selectivity toward OfHex1 over human
β-N-acetylhexosaminidase B (HsHexB) and human O-GlcNAcase (hOGA). In addition, to investigate the basis
for the potency of glycosylated naphthalimides against OfHex1, molecular
docking and molecular dynamics simulations were performed to study
possible binding modes. Furthermore, the in vivo biological
activity of target compounds with efficient OfHex1 inhibitory potency
was assayed against Myzus persicae, Plutella xylostella, and O. furnacalis. This present work indicates that glycosylated naphthalimides can
be further developed as potential pest control and management agents
targeting OfHex1.