含1,3,4-口恶二唑查尔酮衍生物的设计、合成、抗病毒活性及相互作用研究

Design, synthesis, antiviral activity of chalcone derivatives containing the 1,3,4-oxadiazole moiety and their interactions with tobacco mosaic virus coat protein

烟草花叶病毒(tobacco mosaic virus,TMV)是一种常见的植物病毒,能侵染多种农作物,给农业生产造成了巨大损失.本文以查尔酮为先导结构,设计合成了26个新型的含1,3,4-噁二唑查尔酮衍生物,活体抗病毒活性测试表明该类化合物对烟草花叶病毒具有较高的抑制活性,其中化合物C24对TMV表现出最好的抑制活性,其EC_(50)值为20.9μg/mL,明显优于对照药剂宁南霉素(37.9μg/mL).为了初步揭示化合物抗病毒活性的作用机制,利用MST技术测定了化合物C24与TMV CP的结合能力,其解离常数K_d值为9.05μM,说明化合物C24与TMV CP强结合后制约了TMV CP自组装,进而抑制TMV病毒对寄主的侵染.

Tobacco mosaic virus（TMV） is one of well-studied plant viruses, which can infect various crops and cause huge losses to agricultural production. Twenty-six chalcone derivatives containing the 1,3,4-oxadiazole moiety were synthesized base on the lead compound chalcone. Bioassays showed that most of the compounds exhibited good inhibitory activities against TMV in vivo. Among them, compound C24 demonstrated excellent activities against TMV with EC_（50）values of 20.9 μg/m L, better than ningnanmycin（37.9 μg/m L）. In order to preliminarily reveal the interactions between high-activity compound and TMV CP, the combining capacity of C24 to TMV CP was tested by MST. The result showed C24 has higher binding affinity to TMV CP with a dissociation constant（K_d） of 9.05 μM, which restricts TMV CP self-assembly and inhibits TMV from infecting the host.