[Quality-based soil fertility quality assessment of American ginseng main production areas in Shandong province].

The soil fertility quality is one of the most critical indicators of soil productivity. It directly affects the yield, quality and agricultural efficiency of Chinese medicinal materials. In order to establish the American ginseng planting soil fertility quality evaluation method based on the effective components of American ginseng, Wendeng district, Weihai city, Shandong province, the main producing area of American ginseng, was cited as a case for the study. Twenty-two 4-years American ginseng sampling sites are located at 7 towns. The samples of soil and plant root were collected in the autumn of 2017-2019. The saponin contents of American ginseng and 11 soil chemical properties were measured. The minimum data set(MDS) for assessment of the quality of soil fertility quality was established by correlation analysis and principal component analysis. The evaluation indexes were normalized by membership function. Soil quality index(SQI) that indicates soil comprehensive fertility quality level was calculated according to the critical value of membership function and weight value of each soil index in MDS. The results showed that the total saponin(Rg_1+Re+Rb_1) content of American ginseng in samples ranged from 1.76% to 7.94%. The yield of 8 plots in 2019 ranged from 3 818.7 kg·hm~(-2) to 8 996.4 kg·hm~(-2). MDS includes organic matter, alkaline nitrogen, exchangeable calcium, exchangeable magnesium, effective iron, effective copper, and effective zinc. Based on the mean of 4.825% of total saponin, threshold value of SQI for the region was determined to be 0.15, and 86.36% of soil samples in the county were above the threshold value. The methods and parameters are applicable to selection of high quality American ginseng planting sites and guiding rational fertilization. It also provides a reference for the evaluation of soil fertility quality of other medicinal plants.

Determination of purity of a new anti-fatty liver drug IMH by differential scanning calorimetry method and uncertainty evaluation / 药学学报

The purity of 4,4′-dimethoxy-5,6,5′,6′-bis (methylenedioxy)-2′-morpholine methylenebiphenyl-2-methyl formate methanesulfonate (IMH), a new drug for fatty liver treatment, was determined through differential scanning calorimetry (DSC). Analysis of two-factor non repeatability method was performed in the investigation the effects of two factors (heating rate and sample weight) on purity determination. The DSC experimental parameters were optimized as follows: heating rate was 10 ℃·min-1, temperature range was 150-300 ℃, sample weight was 2.0-4.1 mg, and N2 flow rate was 80 mL·min-1. The linear correlation coefficient (r) of this DSC method was 0.999 8. The RSD value (n = 6) of precision was 0.03%. The standard value and uncertainty of the purity results of the multiple batches of IMH drugs were (99.74 ± 0.29)%, (99.91 ± 0.28)%, (99.90 ± 0.28)%, and (99.81 ± 0.28)% with inclusion factor (K) of 2 and confidence probability (P) of 0.95. The results were basically consistent with the results of the mass balance method. The DSC mehod is a simple, rapid and accurate method, and provides a new reference method for determining the purity of IMH drugs, improves the accuracy and reliability of purity determination.

Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.