Design, Synthesis, Anti-Tomato Spotted Wilt Virus Activity, and Mechanism of Action of Thienopyrimidine-Containing Dithioacetal Derivatives

Currently, there is insufficient viricide to effectively control tomato spotted wilt virus (TSWV). To address this pending issue, a series of thienopyrimidine-containing dithioacetal derivatives were prepared and tested for their anti-TSWV activities. A subsequent three-dimensional quantitative structure–activity relationship was constructed to indicate the development of optimal compound 35. The obtained compound 35 had excellent anti-TSWV curative, protective, and inactivating activities (63.0, 56.6, and 74.1%, respectively), and the EC50 values of protective and inactivating activities of compound 35 were 252.8 and 113.5 mg/L, respectively, better than those of ningnanmycin (284.8 and 144.7 mg/L) and xiangcaoliusuobingmi (624.9 and 300.0 mg/L). In addition, the anti-TSWV activity of compound 35 was associated with defense-related enzyme activities, enhanced photosynthesis, and reduced stress response, thereby enhancing disease resistance.

目前尚无能够有效防控番茄斑点萎蔫病毒（TSWV）的杀病毒剂。为解决这一亟待攻克的技术难题，本研究合成了一系列含噻吩并嘧啶的二硫缩醛类衍生物，并对其抗番茄斑点萎蔫病毒活性进行了测试。随后构建了三维定量构效关系模型，以指导优化化合物35的开发。所得化合物35展现出优异的抗TSWV治疗、保护与钝化活性，分别为63.0%、56.6%与74.1%；其保护活性与钝化活性的半有效浓度（EC₅₀）分别为252.8 mg/L和113.5 mg/L，优于宁南霉素的284.8 mg/L和144.7 mg/L以及香曹柳苏bingmi（xiangcaoliusuobingmi）的624.9 mg/L和300.0 mg/L。此外，化合物35的抗TSWV活性与其调控防御相关酶活性、增强光合作用以及降低胁迫响应密切相关，进而提升植株的抗病能力。