文献类型：期刊文献

英文题名：Halichonine B Inspired Design and Divergent Optimization of Drimanyl Amine for Novel Antimicrobial Leads

作者：Hu, Nvdan Sun, Shengxin Ming, Xian Li, Shengkun

第一作者：胡女丹;Hu, Nvdan

通信作者：Li, SK[1]

机构：[1]Guizhou Univ, State Key Lab Green Pesticide, Ctr R&D Fine Chem, Guiyang 550025, Peoples R China;[2]Guizhou Inst Technol, Coll Food & Pharmaceut Engn, Guiyang 550003, Guizhou, Peoples R China

第一机构：Guizhou Univ, State Key Lab Green Pesticide, Ctr R&D Fine Chem, Guiyang 550025, Peoples R China

通信机构：corresponding author), Guizhou Univ, State Key Lab Green Pesticide, Ctr R&D Fine Chem, Guiyang 550025, Peoples R China.

年份：2025

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001568908800001)】；

基金：This work was financially supported by the Guizhou Provincial Science and Technology Projects (ZK[2023]Key Program 008) and the National Natural Science Foundation of China (22477019).

语种：英文

外文关键词：drimanyl amine; linker; function-oriented optimization; antimicrobial leads; structure-activity relationship

摘要：Structurally unique halichonine B is promising for the design of pharmaceutical leads, while function-oriented optimization is unknown in agrochemical science. Our recent practical synthesis offers a great chance for the discovery of antimicrobial leads. "Linker plus replaceable substituents" is exerted, in which up to 9 unique linkers together with diverse substituents from a wide chemical space are investigated for optimization of the readily available drimanyl amine. The diamine- or amino amide-related C-2- or C-3-linker is preferred for increasing the bioactive potency. N,N '-bis(substituted) ethylenediamine 5a exhibited significant activity against Phytophthora capsici with the effective concentration (EC50) value of 9.91 mu M. 2-Amino-drimanylacetamides 3n (EC50 = 7.27 mu M) and 3s (EC50 = 6.42 mu M) are selected as leads against Sclerotinia sclerotiorum. Compounds 3t and 4i were highly potent against fungal, oomycete, and bacterial plant pathogens and bacterial foodborne pathogens in vitro. The EC50 value of 4i was 5.31 mu M against Ralstonia solanacearum, demonstrating >18-fold improvement over that of the commercial antibacterial agent thiodiazole-copper. It demonstrated a pronounced inhibitory effect on the swarming motility and biofilm formation of R. solanacearum. Beneficial properties are acquired for promising leads 4i, 3n, and 5a through cheminformatics analysis. Synthetically tractable optimization of linkers could augment lead identification and may play an extraordinary role in optimizing and expanding the chemical space of drimanyl amine, further enhancing its impact on lead discovery.