Antiviral activity evaluation and action mechanism of chalcone derivatives containing phenoxypyridine.

In this paper, a series of phenoxypyridine-containing chalcone derivatives (L1-L28) were designed and synthesized, characterized on NMR and HRMS. Ningnanmycin (NNM) was used as a control agent. The results of the antiviral activity testing showed that the curative activity EC50 values of L1 and L4 against TMV were 140.5 and 90.7 µg/mL, respectively, which were superior to that of NNM (148.3 µg/mL). The EC50 values of 154.1, 102.6 and 140.0 µg/mL for the anti-TMV protective activities of L1, L4 and L15 were superior to that of NNM (188.2 µg/mL). The mechanism of action between L4 and NNM and tobacco mosaic virus capsid protein (TMV-CP) was preliminarily investigated. The results of microscale thermophoresis (MST) experiments showed that L4 had a strong binding affinity for TMV-CP with a dissociation constant Kd value of 0.00149 µM, which was better than that of NNM (2.73016 µM). The results of molecular docking experiments showed that L4 formed shorter hydrogen bonds with amino acid residues of TMV-CP than NNM and formed more amino acid residues than NNM, which indicated that L4 was more tightly bound to TMV-CP. This study suggested that phenoxypyridine-containing chalcone derivatives can be used as new anti-TMV drugs through further research and development.

Design, synthesis, and bioactivity studies of chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine.

In this study, 30 chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine were designed and synthesized. The results of antibacterial activity showed that EC50 values of N26 against Xoo, Pcb was 36.41, 38.53 µg/mL, respectively, which were better than those of thiodiazole copper, whose EC50 values were 60.62, 106.75 µg/mL, respectively. The bacterial inhibitory activity of N26 against Xoo was verified by SEM. Antibacterial mechanism between N26 and Xoo was preliminarily explored, the experimental results showed that when the drug concentration was 100 mg/L, N26 had a good cell membrane permeability of Xoo, and it can inhibit the production of EPS content and extracellular enzyme content to disrupt the integrity of the Xoo biofilms achieving the effect of inhibiting Xoo. At 200 mg/L, N26 can protect and inhibit the lesions of post-harvested potatoes in vivo. The activities of N1-N30 against TMV were determined with half leaf dry spot method. The EC50 values of the curative and protective activity of N22 was 77.64 and 81.55 µg/mL, respectively, which were superior to those of NNM (294.27, 175.88 µg/mL, respectively). MST experiments demonstrated that N22 (Kd = 0.0076 ± 0.0007 µmol/L) had a stronger binding ability with TMV-CP, which was much higher than that of NNM (Kd = 0.7372 ± 0.2138 µmol/L). Molecular docking results showed that N22 had a significantly higher affinity with TMV-CP than NNM.

[Treatment of ankylosing spondylitis with Zhengqing Fengtongning release tablets: Meta-analysis of randomized controlled trials].

The review aims to assess the effectiveness and safety of Zhengqing Fengtongning release tablets in treating ankylosing spondylitis (AS) systematically through searching relevant electronic databases and collecting relevant literature. Such Chinese databases as CNKI, VIP, Wanfang, and English databases as PubMed, EMbase and Cochrane Library, etc, were searched from the date of their establishment to September 2017. According to the inclusion and exclusion criteria, the methodology quality of included studies was evaluated by two independent reviewer using Cochrance evaluation system, and Meta-analysis on the clinical efficacy and safety of Zhengqing Fengtongning release tablets for AS was conducted with RevMan 5.3 software. Seven randomized control trials (RCTs) including 570 patients of AS were included, with 294 patients in Zhengqing Fengtongning treatment group and 276 patients in the western medicine control group. Meta-analysis showed that: Zhengqing Fengtongning alone treatment was superior to sulfasalazine groups in the effect on improving the total effective rate. Besides, as compared to sulfasalazine control group, the time of morning stiffness and the finger-to-floor distance were significantly shortened in Zhengqing Fengtongning treatment group. However, the cciput-to-wall distance， the chest expansion, Schober's test, disease activity score (DAS) in patients, disease activity score (DAS) in doctors, ESR, CRP showed no statistically significant differences. As compared with western medicine control group, Zhengqing Fengtongning combined with western medicine had a higher total effective, significantly shorten the time of morning stiffness, and increase Schober's test values; However, the cciput-to-wall distance, the finger-to-floor distance, the chest expansion, DAS in patients, DAS in doctors, ESR and CRP showed no statistically significant differences. Zhengqing Fengtongning had less adverse reactions in clinical application, and the main adverse reaction was skin rash or itching when used alone. The study showed: Zhengqing Fengtongning is effective for AS with high safety, but high quality clinical trials are still needed to further prove its clinical efficacy and safety.