Exploiting natural products to discover multitarget inhibitors of insect chitinolytic enzymes

Multitarget insecticides are more likely to achieve comprehensive regulation of insects with a low risk of resistance. Insect chitinolytic enzymes, including GH18 chitinases and GH20 β-N-acetyl-d-hexosaminidase, are attractive targets for multitarget insecticide design by virtue of their similar substrate binding mode and catalytic mechanism. On the other hand, natural products with diverse skeletal structures are potential repositories of chitinolytic enzyme inhibitors. This minireview first presents the theoretical basis of developing multitargeted inhibitors against insect chitinolytic enzymes and then focuses on the progress in developing multitarget inhibitors derived from natural products. These may provide ideas for the exploitation of novel pesticide leads from natural products by targeting multiple targets.