Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.

Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.

Simultaneous Quantitative Analysis of Q-Marker with One Single Reference in Glycyrrhiza uralensis Fisch.

In traditional Chinese medicine (TCM) studies, it is difficult to choose evaluation markers for the strict quality control of herbs. A high performance liquid chromatography coupled with metabolomics for simultaneous quantitative analysis of quality markers (Q-markers) in Glycyrrhiza uralensis Fisch was established, which could not only ensure the quality and batch-to-batch consistency of TCMs, but also achieve a quantitative analysis of multi-components by the single reference standard. Based on the construction of chromatographic profiles by high performance liquid chromatography (HPLC) and HPLC-Q-Exactive/MS methods, different multivariate analyses were employed. Seven quantitative indices were selected as the Q-markers, and a reliable quantification method was established. The quantitative method was acceptable with good linearity with correlation coefficients >0.9993 and satisfactory repeatability (relative standard deviation (RSD) < 0.05%), precision (RSD < 0.24%), reproducibility (RSD < 0.97%), stability (RSD < 2.52%) and recoveries (96.96%-98.52%, RSD < 3.24%), and no significant differences were observed between the external standard method and the new method as determined by calculating standard method difference. Overall, the study suggests that the simultaneous quantitative analysis of main Q-marker in G. uralensis Fisch with one single marker can be considered good quality criteria for performing quality control of G. uralensis Fisch.

Innate factors causing differences in gene flow frequency from transgenic rice to different weedy rice biotypes.

BACKGROUND: The compatibility and outcrossing rates between transgenic rice and weedy rice biotypes have been studied in some previous cases. However, few studies have addressed the reasons for these differences. The present study compared the compatibility and outcrossing rates between transgenic rice and selected weedy rice biotypes using manual and natural crossing experiments to elucidate the key innate factors causing the different outcrossing rates. RESULTS: Hybrid seed sets from manual crossing between transgenic rice and weedy rice varied from 31.8 to 82.7%, which correlated directly with genetic compatibility. Moreover, the significant differences in the quantity of germinated donor pollens and pollen tubes entering the weedy rice ovule directly contributed to the different seed sets. The natural outcrossing rates varied from 0 to 6.66‰. The duration of flowering overlap was the key factor influencing natural outcrossing. Plant and panicle height also affected outcrossing success. CONCLUSION: From this study, it is concluded that the likelihood of gene flow between transgenic rice and weedy rice biotypes is primarily determined by floral synchronisation and secondarily influenced by genetic compatibility and some morphological characteristics.