Design, synthesis, bioactivity and mechanism of dithioacetal derivatives containing dioxyether moiety

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Wang, Yanju¹  Zhang, Jian¹  He, Fangcheng¹  Gan, Xiuhai¹  Song, Baoan¹  Hu, Deyu¹ 

[1] Guizhou Univ, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn, Minist Educ, Guiyang 550025, Guizhou, Peoples R China

关键词: Dithioacetal derivatives;    Vanillin;    Dioxyether moiety;    Antiviral activities;    Transmission electron microscopy;    Interaction;    Molecule docking;   

DOI  :  10.1016/j.bmcl.2019.06.030

来源: Elsevier

【 摘 要 】

The present work designed and synthesized a series of dithioacetal derivatives containing dioxyether, as well as evaluated their antiviral activities against tobacco mosaic virus (TMV). Bioassays demonstrated that the target compounds showed excellent anti-TMV activities in vivo and in vitro. Compound 24c has excellent anti-TMV activities, and its curative, protective and inactivating activities for TMV were 50.9%, 58.9% and 81.8%, respectively, which are obviously superior to those of ribavirin (50.2%, 41.3% and 69.5%, respectively). Moreover, the EC50 of the inactivating activities of the anti-TMV of compound 24c is 67.9 mg/L, which is superior to that of ribavirin (149.5 mg/L). Transmission electron microscopy showed that compound 24c caused great damage to the morphology of TMV particles, causing fracture and bending. Molecule docking model revealed that this compound formed five conventional hydrogen bonds with the active sites of amino acids GLN57, ASN73, TYR139, and SER138. Furthermore, the test results of Fluorescence titration and microscale thermophoresis showed that compound 24c has a strong binding force with TMV coat protein (TMV CP), with an association constant (K-a) of 1.04 x 10(5) L/mol and dissociation constant (K-d) of 1.6 +/- 0.6 mu M. These results indicate that the dithioacetal derivatives containing dioxyether are worthy of further research and development as novel antiviral agents.

【 授权许可】

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