Design, synthesis, structural optimization, and biological activity research of quinazolinone alkaloid isaindigotone

作者：Sijia Liu, Xu Yubin, Manman Li, Zhiying Zhao, Aidang Lu, Hongying Tang, Qingmin Wang, Ziwen Wang · 发表于：Pest Management Science · 年份：2025 · DOI：10.1002/ps.70290 · 被引用次数：1 · 研究领域：Quinazolinone synthesis and applications、Fungal Plant Pathogen Control、Biological Activity of Diterpenoids and Biflavonoids

Abstract BACKGROUND Plant viruses, which are among the most devastating pathogens, cause enormous losses to agricultural industries worldwide and continue to threaten global food security. Current antivirals like ribavirin and ningnanmycin show limited efficacy against plant viruses, underscoring the need for more potent agents. Quinazolinone alkaloids play a vital role in drug discovery. RESULT After an extensive literature survey, we explored a highly efficient and straightforward synthetic route to access isaindigotone. Starting from commercially available deoxyvasicinone, a two‐step sequence delivered the target isaindigotone in an overall yield of 60%. A series of isaindigotone derivatives were designed, synthesized, and evaluated for their bioactivities. We found that these compounds have good to excellent antiviral activities against tobacco mosaic virus (TMV). Most of these compounds exhibited higher anti‐TMV activities than ribavirin. Alkaloid isaindigotone and its derivatives 2b and 2f displayed significantly higher inhibitory effects (half‐maximal inhibitory concentration (IC 50 ): 120–195 μg mL −1 ) than ningnanmycin (IC 50 : 220 μg mL −1 ), thus emerged as novel antiviral candidates. We selected 2f for further antiviral mechanism studies and found that 2f can inhibit viral assembly by interacting with the TMV coat protein (CP). Molecular docking results further confirmed that these compounds can interact with CP through hydrogen bonds. These compounds also demons...