新型苯并[d][1,3]dioxole-6-苯甲酰胺衍生物的设计、合成和生物活性：作为潜在昆虫生长调节剂候选物的多壳多糖酶抑制剂,Journal of Agricultural and Food Chemistry

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新型苯并[d][1,3]dioxole-6-苯甲酰胺衍生物的设计、合成和生物活性：作为潜在昆虫生长调节剂候选物的多壳多糖酶抑制剂
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-05-30 , DOI: 10.1021/acs.jafc.3c00775
Xiaoyu Jin ₁ , Tengda Sun ₁ , Bingbo Guo ₁ , Jialin Cui ₁ , Yun Ling ₁ , Li Zhang ₁ , Qing Yang ₂ , Wei Chen ₂ , Xinling Yang ₁

Affiliation

昆虫生长调节剂 (IGRs) 扰乱昆虫生理过程的正常发育，被公认为绿色杀虫剂。昆虫几丁质酶在蜕皮过程中的角质层降解中起着至关重要的作用，Of ChtI、Of ChtII 和Of Chi-h 是发现新型杀虫剂如 IGRs 的潜在目标。在我们之前的研究中，我们将先导化合物a12鉴定为一种有前途的多靶点抑制剂。在此，我们使用a12与三种几丁质酶的结合模式来识别有利于生物活性的关键相互作用和残基。随后，为了通过增强与重要残基的相互作用来提高抑制剂的生物活性，一系列苯并[ d][1,3]dioxole-6-benzamide衍生物的合理设计和合成，及其对亚洲玉米螟( O. furnacalis )几丁质酶的抑制活性，以及对亚洲玉米螟( O. furnacalis )和小菜蛾( P. xylostella )的杀虫活性。调查。其中，化合物d29同时作用于Of ChtI、Of ChtII和Of Chi-h，K _i值分别为0.8、11.9和2.3 μM，较先导化合物a12的抑制活性有显着提高。此外，d29通过干扰正常的昆虫生长和蜕皮，对两种鳞翅目害虫表现出优于a12的活性，表明d29是具有多壳多糖酶机制的新型 IGR 的潜在主要候选者。本研究表明，同时抑制多种几丁质酶可以获得优异的杀虫活性。抑制机制和分子构象的阐明说明了与三种几丁质酶的相互作用，以及生物活性的差异，这将有利于未来提高生物活性作为IGRs在可持续农业中防治害虫的效力。

"点击查看英文标题和摘要"

Design, Synthesis, and Biological Activity of Novel Benzo[d][1,3]dioxole-6-benzamide Derivatives: Multichitinase Inhibitors as Potential Insect Growth Regulator Candidates

Insect growth regulators (IGRs) disrupt normal development of physiological processes in insects and are recognized as green insecticides. Insect chitinases play a crucial role in cuticle degradation during molting, and OfChtI, OfChtII, and OfChi-h are the prospective targets for discovering new insecticides as IGRs. In our previous study, we identified the lead compound a12 as a promising multitarget inhibitor. Herein, we used the binding modes of a12 with three chitinases to recognize the critical interactions and residues favorable to the bioactivity. Subsequently, to improve the bioactivity of inhibitors via enhanced the interactions with important residues, a series of benzo[d][1,3]dioxole-6-benzamide derivatives were rationally designed and synthesized, and their inhibitory activities against Ostrinia furnacalis (O. furnacalis) chitinases, as well as insecticidal activities against O. furnacalis and Plutella xylostella (P. xylostella) were investigated. Among them, compound d29 acted simultaneously on OfChtI, OfChtII, and OfChi-h with K_i values of 0.8, 11.9, and 2.3 μM, respectively, a significant improvement over the inhibitory activity of the lead compound a12. Moreover, d29 exhibited superior activity than a12 against two lepidopteran pests by interfering with normal insect growth and molting, indicating that d29 is a potential lead candidate for novel IGRs with a multichitinase mechanism. The present study revealed that simultaneous inhibition on multiple chitinases could achieve excellent insecticidal activity. The elucidation of inhibition mechanisms and molecular conformations illustrated the interactions with the three chitinases, as well as the discrepancy in bioactivity, which will be beneficial for future work to improve the potency of bioactivity as IGRs for pest control in sustainable agriculture.

更新日期：2023-05-30

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