数字农科院2.0

Discovery of multi-chitinase inhibitors cinnamyl thiazolidinone compounds as candidates for insect growth regulators via ligand-based optimization strategies

文献类型： 外文期刊

作者： Zhiyang Jiang;Dongmei Shi;Haoyu Fu;Yan Li;Renxuan Zou;Ziqi He;Jie Shi;Lijuan Shen;Bin Tang;Zhijian Xu;Qing Yang;Hongxia Duan

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关键词： Cinnamaldehyde compounds;Insect growth regulators (IGRs);Ligand-based optimization;Multi-chitinase inhibitor;Thiazolidinone compounds

期刊名称： International Journal of Biological Macromolecules

ISSN： 0141-8130

年卷期： 2025 年 306 卷

页码：

收录情况： SCIE（2025版） ; ; EI（2025版）

摘要： Chitinases are recognized as potential targets to develop novel insecticides to control lepidopteran pests. However, the design and development of effective multi-chitinase inhibitors remains a huge challenge. Based on the backgrounds, in this study, we designed and synthesized a series of cinnamyl-thiazolidinedione compounds as potential inhibitors against OfChtI, OfChtII and OfChi-h, for the first time, by integrating strategies including fragment replacement, 3D QSAR-guided design, and bioelectronic isosteric replacement. Among all synthesized compounds, those displayed substantial activities against three chitinases, such as 5f and 9m, simultaneously demonstrated significant larvicidal activities and growth regulation effects against various lepidopteran pests. Inhibition mechanism studies indicated that the π interactions, hydrophobic stacking, and electrostatic interactions between cinnamyl-thiazolidinone compounds and the conserved aromatic tryptophan and phenylalanine residues, as well as the polar asparagine residues in three chitinases, were crucial for their interactions. Furthermore, the qPCR experiment suggested that cinnamyl-thiazolidinone compounds could regulate the chitin metabolism pathway of Ostrinia furnacalis in vivo. This study provides the first successful example of developing novel multi-chitinase inhibitors through ligand-based optimization strategies, offering promising candidates for controlling lepidopteran pests.

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