Junyu Liang

Synthesis and characterisation of seleno-Cynomorium songaricum Rupr. polysaccharide

In this article, the structural properties of Cynomorium songaricum Rupr. polysaccharide (CSP) after selenylation were investigated. The crude polysaccharide was obtained from C. songaricum Rupr. by water extraction followed by ethanol precipitation and freeze vacuum drying. Then selenylation of CSP has been accomplished by employing sodium selenite to modify the polysaccharide under the catalysis of nitric acid–barium chloride. After selenylation, the sugar content and the molecular weight increased but the protein content reduced. The maximum selenic content determined by ICP-AES was 2925 µg g−1. The selenide CSP (Se-CSP) was characterised by the methods of UV spectra, FT-IR, Raman spectra and X-ray photoelectron spectroscopy. The results showed that the hydroxyl hydrogen of the sugar moieties was substituted by Se=O. Thermal stability of Se-CSP was also measured by TG-DTA.

Novel naïve Bayes classification models for predicting the chemical Ames mutagenicity

Prediction of drug candidates for mutagenicity is a regulatory requirement since mutagenic compounds could pose a toxic risk to humans. The aim of this investigation was to develop a novel prediction model of mutagenicity by using a naïve Bayes classifier. The established model was validated by the internal 5-fold cross validation and external test sets. For comparison, the recursive partitioning classifier prediction model was also established and other various reported prediction models of mutagenicity were collected. Among these methods, the prediction performance of naïve Bayes classifier established here displayed very well and stable, which yielded average overall prediction accuracies for the internal 5-fold cross validation of the training set and external test set I set were 89.1±0.4% and 77.3±1.5%, respectively. The concordance of the external test set II with 446 marketed drugs was 90.9±0.3%. In addition, four simple molecular descriptors (e.g., Apol, No. of H donors, Num-Rings and Wiener) related to mutagenicity and five representative substructures of mutagens (e.g., aromatic nitro, hydroxyl amine, nitroso, aromatic amine and N-methyl-N-methylenemethanaminum) produced by ECFP_14 fingerprints were identified. We hope the established naïve Bayes prediction model can be applied to risk assessment processes; and the obtained important information of mutagenic chemicals can guide the design of chemical libraries for hit and lead optimization.

Development of novel in silico model for developmental toxicity assessment by using naïve Bayes classifier method

Toxicological testing associated with developmental toxicity endpoints are very expensive, time consuming and labor intensive. Thus, developing alternative approaches for developmental toxicity testing is an important and urgent task in the drug development filed. In this investigation, the naïve Bayes classifier was applied to develop a novel prediction model for developmental toxicity. The established prediction model was evaluated by the internal 5-fold cross validation and external test set. The overall prediction results for the internal 5-fold cross validation of the training set and external test set were 96.6% and 82.8%, respectively. In addition, four simple descriptors and some representative substructures of developmental toxicants were identified. Thus, we hope the established in silico prediction model could be used as alternative method for toxicological assessment. And these obtained molecular information could afford a deeper understanding on the developmental toxicants, and provide guidance for medicinal chemists working in drug discovery and lead optimization.

Fumigant and repellent activities of essential oil extracted from Artemisia dubia and its main compounds against two stored product pests

Abstract The major chemical constituents of the essential oil extracted from Artemisia dubia wall. ex Bess. (Family: Asteraceae) were found as terpinolene (19.02%), limonene (17.40%), 2,5-etheno[4.2.2]propella-3,7,9-triene (11.29%), isoelemicin (11.05%) and p-cymene-8-ol (5.93%). Terpinolene and limonene were separated as main components from the essential oil. The essential oil showed fumigant toxicity against Tribolium castaneum and Liposcelis bostrychophila with LC50 values of 49.54 and 0.74 mg/L, respectively. The essential oil and isolated compounds of A. dubia showed repellency activities against both insects. Terpinolene and limonene showed the fumigant toxicity against T. castaneum. Terpinolene showed obvious fumigant toxicity against L. bostrychophila. The results indicated that the essential oil of A. dubia had potential to be developed into natural insecticides for controlling stored product pests.

Synthesis and structural features of phosphorylated Artemisia sphaerocephala polysaccharide

Phosphorylation is a key route to achieve varieties of biological activities for polysaccharides. Currently, conventional phosphorylation reagents are characterized by long processing times and high reaction temperatures. Here, we reported phosphorylation of Artemisia sphaerocephala polysaccharides (PASP) with the degrees of substitution (DS) of 0.34-0.54 in mild reaction conditions (3-4h and 25°C) by employing POCl3/pyridine technique. FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS) analysis confirmed the appearance of phosphate ester (P5+) groups in PASP. Size exclusion chromatography combined with multi-angle laser light scattering (SEC-MALLS) result clearly showed temperature-dependent increment of weight average molecular mass (MW). High temperature facilitated the reaction of phosphoryl chloride with primary and secondary hydroxyl groups, favoring the crosslinking of polysaccharide chains by phosphate di-esters as further confirmed in 13C NMR determination. Our results provide insight into the relationship between the structure and reaction conditions of phosphorylated polysaccharide, which is important for understanding and exploiting these derivatives in a wide range of applications.

Sulfation can enhance antitumor activities of Artemisia sphaerocephala polysaccharide in vitro and vivo

In this study, a sulfated Artemisia sphaerocephala polysaccharide (ASPs) was prepared and its antitumor activity was evaluated in tumor cells and Hepatoma 22 (H22) tumor-bearing mice. In vitro experiments, ASPs significantly inhibited the growth of HepG2 and Hela cells with the IC50 values of 172.03 and 161.42μg/mL, respectively. Moreover, no direct cytotoxicity against mouse fibroblast L929 normal cells was observed in vitro. After oral administration for 12days, the tumor growth was significantly suppressed by ASPs at the doses of 200mg/kg (inhibition rate of 60.85%). Results of tumor histological morphology and cell cycle analysis showed that ASPs could arrest H22 cells at S phase and promote cell apoptosis. Additionally, immunohistochemical analysis demonstrated that ASPs caused the down-regulation of mutant p53 protein expression in a dose-dependent manner. Therefore, these findings proposed new insight into antitumor properties of sulfated polysaccharide as a promising agent in cancer treatment.

Efficient synthesis of polysaccharide with high selenium content mediated by imidazole-based acidic ionic liquids

Exploring new solvents or catalysts has great prospect for the derivatization of poorly soluble natural polysaccharides as bio-resources which were extracted from food or industrial waste residue, as compared to traditional reaction system. In this work, selenized Artemisia sphaerocephala polysaccharide (SePAS) was synthesized by using imidazolium-based acidic ionic liquids (AILs) as catalyst. The results showed the highest Se content increased to 20438 μg/g compared to conventional method (1703 μg/g), indicating AILs could enhance selenylation reactivity and Se content was controlled by the acidity due to the protonation effect of H2SeO3 by AILs. FT-IR, X-ray photo-electron spectroscopy (XPS) and 13C NMR results exhibited that seleno-group exists in SePAS and the substitution position was at C-6. The hydrogen bonding effect and acidity of AILs showed regulation on weight average molecular mass of SePAS. Therefore, AILs with excellent catalytic efficiency could be as potential catalyst for full use of polysaccharide-rich resources.

Antagonistic activity of essential oils and their main constituents extracted from Ajania fruticulosa and A. potaninii against Ditylenchus destructor

The antagonistic activities of essential oils of Ajania potaninii and A. fruticulosa against Ditylenchus destructor were determined by the liquid soak method in 96-well microplates. The main constituents of A. potaninii essential oil were 1,8-cineole (22.19%), (+)-camphor (12.84%), (−)-verbenol (13.84%) and borneol (12.67%). The results showed that the essential oils of A. fruticulosa (EC 50 = 0.17 mg ml −1 ) and A. potaninii (EC 50 = 0.27 mg ml −1 ) have antagonistic activity against D. destructor . The results also showed that 1,8-cineole (EC 50 = 0.49 mg ml −1 ), myrtenol (EC 50 = 0.40 mg ml −1 ) ( A. fruticulosa ) and (−)-verbenol (EC 50 = 1.09 mg ml −1 ) ( A. potaninii ) have antagonistic activity. 1,8-Cineole is a key element affecting the antagonistic activity that was found in both essential oils. Several main constituents found in the essential oils had antagonistic effects against D. destructor . These results provide the basis for future development and utilisation of a substance to control D. destructor .

Synthesis and structure characterization of sulfated galactomannan from fenugreek gum

Sulfated derivatives of the galactomannan family have multiple biological activities. In the present study, sulfated galactomannan from fenugreek gum (SFG) were prepared by chlorosulfuric acid/pyridine (CSA/Py) method. In order to acquire the derivatives with the highest degree of substitution (DS), the experiment optimum conditions of the sulfation were determined by Box-Behnken design (BBD). The quadratic regression model analysis confirmed that reaction time was the most significant parameter for the impact of DS. Under the selected conditions, maximum DS was obtained as 0.490. Results of FT-IR and X-ray photoelectron spectroscopy (XPS) indicated the present of SO3- group. In 13C NMR spectroscopy, the original C-6 peaks did not disappear completely and the newly peaks appeared at δ 63.2 and 64.0 illustrating the incomplete substitution were predominantly on C-6 position. After sulfation, size exclusion chromatography combined with multi-angle laser light scattering (SEC-MALLS) detected all the weight average molecular mass (MW) of sulfated derivatives decrease rapidly. The introduction of the electrostatic interaction of negatively charged SO3- groups and the decrease in MW could have a significant effect on its biological activity.

An efficient approach to prepare sulfated polysaccharide and evaluation of anti-tumor activities in vitro

Use of microwave radiation is one of the most potential techniques in polysaccharide derivatives synthesis due to its advantages such as higher yields, milder reaction conditions and shorter reaction times. This study was aimed at producing sulfated polysaccharides by microwave irradiation using polar reagents and solvent. Six sulfated Artemisia sphaerocephala polysaccharide derivatives (SPAS) were obtained by using chlorosulfuric acid/pyridine method in the reaction duration range of 15-300 min at a fixed microwave power of 100W. Synthesis of SPAS under microwave filed was highly effective and characterized by time saving and high degrees of substitution (DS). The chemical structure of SPAS was confirmed by FT-IR and 13C NMR that sulfation had occurred and the substitution position was mainly at C-6. Size-exclusion chromatograph combined with multi-angle laser photometer (SEC-MALLS) data indicated that short reaction time minimized acid-catalyzed degradation of polysaccharide chains. AFM observation demonstrated that low-MW derivative exhibited aggregation of polysaccharide chain as irregular spherical lumps. In anti-tumor activity assays, sulfation of PAS significantly improved the capacity to inhibit tumor cells growth by arresting the cell cycle progress in specific phases. It could be concluded that MW and molecular mass distribution had much greater influence on anti-tumor activities of SPAS against human non-small cell lung cancer A549 cells, human hepatocellular carcinoma HepG2 cells and human cervical cancer Hela cells. Microwave-assisted synthesis might possess widespread application in preparation of new polysaccharide derivatives with rich variety of structural features and bioactivities.