Design, synthesis, and activity of 5-cyano-2-thiacetyl aromatic pyrimidinone as DENV NS5 RdRp inhibitors
10.16438/j.0513-4870.2023-0197
- VernacularTitle:5-氰基-2-硫乙酰芳氨嘧啶酮类DENV NS5 RdRp抑制剂的设计、合成及活性研究
- Author:
Jing-bo WANG
1
;
Chun-yan LI
2
;
Zi-jin ZHAO
1
;
Liu-meng YANG
3
;
Hong-bin ZHANG
1
;
Yong-tang ZHENG
3
;
Yan-ping HE
1
Author Information
1. Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China
2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; College of Pharmacy, Dali University, Dali 671000, China; School of Basic Medicine and Clinic Pharmacy, China Pharmaceutical University, Nanjing 211100, China
3. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
- Publication Type:Research Article
- Keywords:
engue virus NS5 RdRp inhibitor;
synthesis;
anti- dengue virus activity;
molecular docking
- From:
Acta Pharmaceutica Sinica
2023;58(11):3379-3388
- CountryChina
- Language:Chinese
-
Abstract:
To screen novel anti-dengue virus (DENV) NS5 RdRp enzyme inhibitors, a series of 5-cyano-2-thiacetoaryl pyrimidinone compounds were designed and synthesized by molecular hybridization method with HCV NS5B RdRp inhibitor 3jc and ZIKV NS5 RdRp inhibitor 4w as lead compounds. The anti-DENV activity of these compounds was evaluated by MTT assay and plaque assay and five compounds showed anti-DENV activity. The most active compound 7a'k showed better anti-DENV activity than that of the positive control ribavirin (EC50 = 7.86 μmol·L-1 vs EC50 = 18.07 μmol·L-1), and the other four compounds showed almost the same anti-DENV activity as ribavirin. Finally, the prediction and simulation of the binding mode through molecular provided new ideas for the further development of this new DENV NS5 RdRp inhibitor.
