Discovery of Novel Nicotinamide Derivatives by a Two-Step Strategy of Azo-Incorporating and Bioisosteric Replacement,Journal of Agricultural and Food Chemistry

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Discovery of Novel Nicotinamide Derivatives by a Two-Step Strategy of Azo-Incorporating and Bioisosteric Replacement
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-14 , DOI: 10.1021/acs.jafc.4c02999
Yifan Ru ₁ , Wen Fu _{1,

2} , Sifan Guo ₁ , Xiaoyan Li ₃ , Cong Zhou ₁ , Zhiping Xu ₁ , Jiagao Cheng ₁ , Zhong Li _{1,

4} , Xusheng Shao _{1,

4,

5,

6}

Affiliation

Azobenzene moieties can serve as active fragments in antimicrobials and exert trans/cis conversions of molecules. Herein, a series of novel nicotinamide derivatives (NTMs) were developed by employing a two-step strategy, including azo-incorporating and bioisosteric replacement. Azo-incorporation can conveniently provide compounds that can be easily optically interconverted between trans/cis isomers, enhancing the structural diversity of azo compounds. It is noteworthy that the replacement of the azo bond with a 1,2,4-oxadiazole motif through further bioisosteric replacement led to the discovery of a novel compound, NTM18, which made a breakthrough in preventing rice sheath blight disease. A control effect value of 94.44% against Rhizoctonia solani could be observed on NTM18, while only 11.11% was determined for boscalid at 200 mg·L^–1. Further mechanism validations were conducted, and the molecular docking analysis demonstrated that compound NTM18 might have a tight binding with SDH via an extra π–π interaction between the oxadiazole ring and residue of D_Y586. This work sets up a typical case for the united applications of azo-incorporating and bioisosteric replacement in fungicide design, posing an innovative approach in structural diversity-based development of pesticides.

中文翻译：

通过偶氮掺入和生物等排置换的两步策略发现新型烟酰胺衍生物

偶氮苯部分可以作为抗菌剂中的活性片段，并发挥分子的反式/顺式转化。在此，通过采用两步策略开发了一系列新型烟酰胺衍生物（NTM），包括偶氮掺入和生物等排置换。偶氮掺入可以方便地提供可以在反式/顺式异构体之间轻松进行光学互换的化合物，从而增强偶氮化合物的结构多样性。值得注意的是，通过进一步的生物等位置换用 1,2,4-恶二唑基序取代偶氮键，发现了一种新型化合物 NTM18，在预防水稻纹枯病方面取得了突破。在 NTM18 上观察到对立枯丝核菌的防效值为 94.44%，而在 200 mg·L^–1.进行了进一步的机制验证，分子对接分析表明，化合物 NTM18 可能通过噁二唑环和 D_Y586 残基之间额外的 π-π 相互作用与 SDH 紧密结合。这项工作为偶氮掺入和生物等排替代在杀菌剂设计中的联合应用奠定了典型案例，为基于结构多样性的农药开发提出了创新方法。

更新日期：2024-09-14

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