文献类型：期刊文献

英文题名：Wavelength-tunable light regulates binding affinity of histone deacetylase inhibitors via azobenzene Photoswitches

作者：Ru, Yifan[1];Guo, Sifan[1];He, Yu[1];Huang, Xiujuan[1];Zhang, Zhenguo[1];Shi, Lei[1,5];Shao, Xiaoguang[6];Li, Zhong[1,2];Fu, Wen[1];Shao, Xusheng[1,2,3,4]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China;[5]Hangzhou Sinotek Qual & Technol Serv Co Ltd, Hangzhou 310052, Zhejiang, Peoples R China;[6]Agr Comprehens Serv Ctr Xiaqiu Town, Yantai 261433, Shandong, Peoples R China

年份：2026

卷号：221

外文期刊名：PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001779394100001)】；

基金：This work was financially supported by National Natural Science Foundation of China (32472610, 32402439), Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) and the project of National Key Laboratory of Green Pesticide/Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University (SKL-GPL-KF-202405).

语种：英文

外文关键词：Photopharmacology; Azobenzene; Regulation; Trifluoromethyloxadiazole; HDAC; Enzymatic assay

摘要：Fungal histone deacetylases (HDACs) are key epigenetic regulatory enzymes, which have emerged as novel targets for pesticide development, involved in phytopathogen growth, development and virulence expression. Photopharmacology offers a promising strategy for developing precision fungicides to mitigate pesticide resistance and non-selective toxicity. Herein, a series of azobenzene-trifluoromethyloxadiazoles (ABTs) photoresponsive HDAC inhibitors were rationally designed and synthesized. Systematic assays were conducted to verify the light-regulable biological activity of the target compounds and against fungal class II HDAC (HdaA). ABT02 exhibited the most remarkable photoregulatory effect, with EC50 of 1.95 mg center dot L-1 in the dark and 9.47 mg center dot L1 after irradiation (4.9-fold difference) against Phakopsora pachyrhizi; Its HdaA enzyme inhibitory IC50 was 0.057 mu M, which is comparable to flufenoxadiazam, with an 8.9-fold activity reduction post-irradiation, and it also mediated light-dependent regulation of spore germination, ROS accumulation and apoptosis. ABT05 realized visible-light (blue and green, 470/520 nm) trans-cis isomerization, overcoming the UV light dependence of traditional azobenzene, and its HdaA inhibitory activity decreased 6.1-fold after illumination, with the IC50 shifting from 1.36 mu M to 8.34 mu M. Molecular docking and electrostatic potential analysis further elucidated the underlying mechanism of photoregulatory activity difference. This study successfully enriches the structural library of photochromic ligands and advances the understanding of target-ligand interactions for fungal HDAC.