Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms
文献类型：期刊论文
| 作者 | Jiang, Zhiyang3,4; Shi, Dongmei3,4; Chen, Yitong2; Li, Huilin3,4; Wang, Jin 'e3,4; Lv, Xinrui3,4; Zi, Yunjiang3,4; Wang, Dongli2; Xu, Zhijian1 ; Huang, Jiaxing3,4
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2023-11-15 |
| 卷号 | 260页码:14 |
| ISSN号 | 0223-5234 |
| 关键词 | Rice blast Trehalose-6-phosphate synthase Isopropanolamine compounds Inhibitor Fungicidal mechanism |
| DOI | 10.1016/j.ejmech.2023.115755 |
| 通讯作者 | Liu, Junfeng(jliu@cau.edu.cn) ; Duan, Hongxia(hxduan@cau.edu.cn) |
| 英文摘要 | The resistance and ecotoxicity of fungicides seriously restrict our ability to effectively control Magnaporthe oryzae. Discovering fungicidal agents based on novel targets, including MoTPS1, could efficiently address this situation. Here, we identified a hit VS-10 containing an isopropanolamine fragment as a novel MoTPS1 inhibitor through virtual screening, and forty-four analogs were synthesized by optimizing the structure of VS-10. Utilizing our newly established ion-pair chromatography (IPC) and leaf inoculation methods, we found that compared to VS-10, its analog j11 exhibited substantially greater inhibitory activity against both MoTPS1 and the pathoge- nicity of M. oryzae. Molecular simulations clarified that the electrostatic interactions between the bridging moiety of isopropanolamine and residue Glu396 of contributed significantly to the binding of j11 and MoTPS1. We preliminarily revealed the unique fungicidal mechanism of j11, which mainly impeded the infection of M. oryzae by decreasing sporulation, killing a small portion of conidia and interfering with the accumulation of turgor pressure in appressoria. Thus, in this study, a novel fungicide candidate with a unique mechanism tar - geting MoTPS1 was screened and discovered. |
| WOS关键词 | TREHALOSE BIOSYNTHESIS ; PLANT INFECTION ; PATHWAY ; PATHOGENICITY ; METABOLISM ; SYNTHASE ; TREHALOSE-6-PHOSPHATE ; TRICYCLAZOLE ; PHOSPHATASE ; INSIGHTS |
| 资助项目 | National Key R amp; D Program of China[2022YFD1700200] ; National Natural Science Foundation of China[31972289] ; National Natural Science Foundation of China[32172445] ; National Natural Science Foundation of China[31772207] ; Chinese Universities Scientific Fund |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| WOS记录号 | WOS:001071524700001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307167]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Liu, Junfeng; Duan, Hongxia |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.China Agr Univ, Coll Plant Protect, Dept Plant Pathol, Beijing 100193, Peoples R China 3.China Agr Univ, Key Lab Natl Forestry & Grassland Adm Pest Chem Co, Beijing 100193, Peoples R China 4.China Agr Univ, Coll Sci, Innovat Ctr Pesticide Res, Dept Appl Chem, Beijing 100193, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Zhiyang,Shi, Dongmei,Chen, Yitong,et al. Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,260:14. |
| APA | Jiang, Zhiyang.,Shi, Dongmei.,Chen, Yitong.,Li, Huilin.,Wang, Jin 'e.,...&Duan, Hongxia.(2023).Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,260,14. |
| MLA | Jiang, Zhiyang,et al."Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 260(2023):14. |
入库方式： OAI收割
来源：上海药物研究所
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