Design, synthesis, and activity of 5-cyano-2-thiacetyl aromatic pyrimidinone as DENV NS5 RdRp inhibitors / 药学学报

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.

Research on chemical constituents from Re-Du-Ning Injection (III) / 中草药

Objective: To study the antiviral constituents from the active fraction of Re-Du-Ning (RDN) Injection. Methods: In this study, the active fraction of RDN Injection was screened by the mice model loaded with restraint stress infected with influenza virus. The chemical constituents were isolated by chromatography on silica gel, ODS, Sephadex LH-20 & Toyopearl HW-40 columns, and reverse phase MPLC & HPLC repeatedly. Their structures were identified by spectral data and physicochemical property. Results: The 95% ethanol eluate of RDN Injection on the macroporous adsorption resin column was proved to be the antivirus active fraction of RDN Injection. Fourteen compounds were isolated and identified as (2E,6S)-8-[α-L-arabinopyranosyl-(1″-6')-β-D-glucopyranosyloxy]- 2,6-dimethylct-2-eno-1,2″-lactone (1), lyoniresinol (2), 5'-methoxyisolariciresinol (3), ent-isolariciresinol (4), (7R,8R)-4,7,9,9'- tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (5), (7S,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (6), ceplignan (7), 5'-methoxyceplignan (8), (-)-dihydrodehydrodiconiferyl alcohol (9), (7S,8R)-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan-4,9,9'-triol (10), (2-cis, 4-trans)-abscisic acid (11), (2-trans, 4-trans)-abscisic acid (12), (1S,3R,4R,5S,7R,9R)-decane-6-carboxylic acid (13), and (1S,3R,4S,5S,7R,9R)-decane-6-carboxylic acid (14); Among them, compound 1 exhibited the antivirus activity against Dengue virus. Conclusion: Compound 8 is a new compound and the other isolated compounds are reported from RDN Injection for the first time, and compound 1 shows the anti-virus activity against Dengue virus.