Synthesis and antibacterial activity of D-glucosamine-fluoroquinolone derivatives / 药学学报

Based on the idea of modification of sugar drugs, or transforming other active substances with sugar molecules, sixteen D-glucosamine-fluoroquinolone (FQ) derivatives were designed by combining D-glucosamine with FQs and synthesized by a multi-step reaction with shared intermediates. The assay results of anti-human pathogenic bacteria and anti-citrus canker showed that the inhibitory activities of two target molecules TM2b and TM2d against Staphylococcus aureus ATCC14125 were stronger than those of all tested positive control drugs, and the inhibitory rates of target molecules TM2m and TM2n against citrus canker were higher than that of the positive control streptomycin at the concentrations of 0.5 and 0.2 µg·mL-1, respectively, which all were worthy of further study. In this study, a series of novel molecules composed of D-glucosamine and FQs were synthesized for the first time, and super antibacterial molecules were found, which expanded the types and biological activities of D-glucosamine derivatives.

Synthesis and Anti-HIV-1 Activity of One Schiff Base Derivative with Glucosamine of Gossypol / 中国药师

Objective: To confirm the structure and preferential conformation of the Schiff base of gossypol with 1, 3, 4, 6-tetra-O-acetyl-β-D-glucosamine and explore its anti-HIV-1 activity.Methods: The Schiff base of gossypol with 11, 3, 4, 6-tetra-O-acetyl-β-D-glucosamine was synthesized and identified by FT-IR, NMR spectroscopy and the PM6 semi-classical calculation.The inhibitory activity of the novel compound against the laboratory-adapted HIV-1IIIB strain was examined using the HIV-1IIIB/TZM-bl indicator cell culture system.Results: The 1H and 13C-NMR signals of the new Schiff base were assigned.The PM6 semi-classical calculation indicated that enamine-enamine tautomeric form of the new Schiff base was more stable,which was stabilized by the intramolecular hydrogen bonds.The anti-HIV-1 test showed that the compound could block the entry of HIV-1IIIB into the target cells.Conclusion: The Schiff base of gossypol with 1, 3, 4, 6-tetra-O-acetyl-β-D-glucosamine exhibits enamine-enamine tautomeric form in solution, which shows potential anti-HIV-1 activity.

Purification of a novel chitin-binding lectin with antimicrobial and antibiofilm activities from a Bangladeshi cultivar of potato (Solanum tuberosum).

A new chitin-binding lectin was purified from a Bangladeshi cultivar ‘Deshi’ of potato (Solanum tuberosum L.) through anion-exchange and affinity chromatographies using a chitin column. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed the molecular mass of the lectin as 20,000 Daltons. This molecular mass was almost half of the molecular masses of chitin-binding lectins derived from other potatoes. The lectin showed both bactericidal and growth-inhibiting activities against Gram-positive (Listeria monocytogenes) and Gram-negative (Escherichia coli, Salmonella enteritidis and Shigella boydii) pathogenic bacteria. It also showed antifungal activity against Rhizopus spp., Penicillium spp. and Aspergillus niger. Biofilm produced by the bacterium Pseudomonas aeruginosa was dose-dependently reduced by 5-20% in 24 h after administration of the lectin, which was attributed to the glycan-binding property of the lectin having affinity to GlcNAc polymers. It was the first observation that any potato lectin prevented biofilm formation by P. aeruginosa and, therefore, could have possible applications in clinical microbiology and biomedical science.

In vitro oxidant effects of D-glucosamine reduce adhesión and biofilm formation of Staphylococcus epidermidis / Los efectos oxidantes de la D-glucosamina in vitro reducen la adhesión y formación de biofilms de Staphylococcus epidermidis

Staphylococcus epidermidis is a common pathogen in medical device-associated infections. Its major pathogenic factor is the ability to form adherent biofilms. In this work, three S. epidermidis strains isolated from infected catheters were chosen with the objective of investigating the effect of D-glucosamine (D-Glu) on reactive oxygen species (ROS) production, adhesion and biofilm formation. The chemiluminescence and nitroblue tetrazolium reduction assays were used to determine ROS production by planktonic S. epidermidis and the microtiter plate assay to quantify in vitro biofilm formation. D-Glu generated a dose-dependent increase in ROS in planktonic cells with maximum stimuli at a concentration of 0.05 mM, and reduced adhesion and biofilm formation. On the other hand, glucose showed an antioxidative stress action and promoted biofilm adhesion and growth. This study suggests a potential application of D-Glu against infections associated with indwelling medical devices, since the oxidative stress caused by this hexosamine in planktonic S. epidermidis contributed to reducing biofilm formation.

Staphylococcus epidermidis es un patógeno común en infecciones asociadas a dispositivos médicos. Su factor de patogenicidad más importante es la capacidad para formar biofilms. Se trabajó con tres cepas de S. epidermidis aisladas de catéteres, con las que se efectuaron ensayos de quimioluminiscencia y de reducción de azul de nitrotetrazolio, para determinar la producción de especies reactivas del oxígeno (ERO) en S. epidermidis planctónico, y ensayos dirigidos a cuantificar la formación de biofilm in vitro, empleando placas multipocillos. La D-glucosamina generó un aumento dependiente de la dosis en la producción de ERO en las células planctónicas, con un estímulo máximo a una concentración de 0,05 mM. Este aumento condμlo a la reducción de la adhesión y de la formación de biofilm. La adición de glucosa, en cambio, mostró un efecto anti estrés oxidativo y promovió la adhesión y el crecimiento de biofilm. Este estudio sugiere una posible aplicación de la D-glucosamina contra las infecciones asociadas a dispositivos médicos, ya que el estrés oxidativo provocado por esta hexosamina contribuyó a una menor formación de biofilm.

Participation of N-acetyl-D-glucosamine carbohydrate moieties in the recognition of Schistosoma mansoni sporocysts by haemocytes of Biomphalaria tenagophila

Lectin-carbohydrate binding may be involved in the recognition of Schistosoma mansoni sporocysts by haemocytes of Biomphalaria; therefore, we tested if this interaction is associated with snail resistance against Schistosoma infection. In vitro data showed that most of the S. mansoni sporocysts cultured with haemocytes from Biomphalaria glabrata BH, a highly susceptible snail strain, had a low number of cells that adhered to their tegument and a low mortality rate. Moreover, the addition of N-acetyl-D-glucosamine (GlcNAc) did not alter this pattern of adherence and mortality. Using haemocytes and haemolymph of Biomphalaria tenagophila Cabo Frio, we observed a high percentage of sporocysts with adherent cells, but complete encapsulation was not detected. Low concentrations of GlcNAc increased haemocyte binding to the sporocysts and mortality, which returned to basal levels with high concentrations of the carbohydrate. In contrast, haemocytes plus haemolymph from B. tenagophila Taim encapsulated cellular adhesion index of level 3 and destroyed over 30 percent of the S. mansoni sporocysts in culture. Interestingly, the addition of GlcNAc, but not mannose, to the culture medium resulted in the significant inhibition of cellular adhesion to the parasite tegument and the reduction of parasite mortality, suggesting that GlcNAc carbohydrate moieties are important to the recognition of S. mansoni by B. tenagophila Taim.

Treatment of diarrhea-predominant irritable bowel syndrome with N-acetyl-D-glucosamine: A randomized, double-blind, placebo-controlled multi-center study Coorperative group / 中华消化杂志

Objective To evaluate the efficacy and safety of N-acetyl-D-glucosamine in treatment of diarrhea-predominant irritable bowel syndrome (D-IBS). Methods A multi-center, randomized, double-blind, placebo-controlled clinical study was performed in 430 patientswith D-IBS. After 2-week baseline period, eligible subjects were randomly either received 100 mg of N-acetyl-D-glucosamine (treated group,n=323) or placebo (control group,n= 107) 3 times a day for consecutive 4 weeks, followed by 2-week withdrawal follow-up. The major parameters were assessed by visual analogue scale (VAS) score and Common Symptom Sensation score. The minor parameters included abdominal pain or discomfort, severity of diarrhea, bloating, urgency, defecation frequencies with consistency per bowel movement which was judged by bristol stool scale and utilization of Smect. The evidence of adverse events was reeoded. Results The major parameters were singnifieantly improved in the treated group with effective rate of 65.16 % at the fourth week of treatment in comparison with control group (effective rate of 34. 29% ,P<0.01). Except the utilization of Smect (P= 1.00), the other minor parameters were significantly improved in treated group compared with control group (P< 0.01) after 1 week treatment. The occurrence of adverse events was 0.96% in the treated group and 0. 95% in the control group (P = 1. 00). Conclusions The results indicate that N-acetyl-D-glucosamine is effective and safe in the treatment of D-IBS by improving ecological environment and preventing activation of mast cells.

Regulation of N-Acetyl-D-glucosamine on macrophages function of stressed mice / 第三军医大学学报

Objective To investigate the regulative role of N-Acetyl-D-glucosamine(GlcNAc) on the stressed mice macrophages function.Methods The stressed mice model was established by electric footshock method.The mice were divided into 5 groups:normal control group,stressed mice model group,low dose Glc-NAc treatment group(0.25 ml 15% GlcNAc),medium-dose GlcNAc treatment group(0.5 ml 15% GlcNAc) and high-dose GlcNAc treatment group(1 ml 15% GlcNAc).GlcNAc was intragastrically injected to corresponding mice 2 h before the electrical stimulation.Peritoneal macrophage(PM?) phagocytosis capability was detected by phagocytosis saccharomycete assay,and PM? energy metabolism was detected by MTT assay.Results Compared with normal control group,stressed mice PM? phagocytosis capability was significantly lower(P

Studies on Elimination of H_2O_2 by D-glucosamine-Cu (Ⅱ) Complex / 中国海洋药物

Objective To study the catalytic capability of glucosamirie-Cu( Ⅱ) complex for decomposition of H2O2 and its relative factors. Methods Glucosamine-Cu( Ⅱ ) complex was prepared by the reaction of D-glucosamine hydrochloride with Cu2+ in aqueous solution, then added it into H2O2 solution. The concentration of H2O2 was determined by titrimetric analysis in a regular interval of time, the rate of decomposition of H2O2 was obtained in various conditions. Results Strong catalytic capability of glucosamine-Cu( Ⅱ ) complex was obtained at 30℃ pH 6. 5, the rate of decomposition was over 90% after 12h, and was almost 100% after 24h. Conclusion The complex of glucosamine-Cu( Ⅱ ) showed good catalytic capability for decomposition of H2O2.

Chemical modification of D-glucosamine and its application in biology and medicine / 中国海洋药物

D-glucosamine has biological activity. The progress in study and application of D-glucosamine derivatives in the field of biology and medicine was reviewed in this paper.

Effects of D-glucosamine hydrochloride on the cell-cycle and expression of proteins in gastric carcinoma cell SGC-7901 / 中国海洋药物

Objective To study the effects of D-glucosamine hydrochloride on the apoptosis of gastric carcinoma cell line SGC-7901 and its mechanism.Methods SRB assay was used to examine the effects of D-glucosamine hydrochloride on the growth inhibition of SGC-7901.The cell-cycle and expression of cytochrome-C were observed by flow cytometry,the concentrations of intracellular Ca2+ was determined by CLSM and the expressions of cyclinB1,calcinerin were investigated by Western-Blot.Results D-glucosamine hydrochloride could block SGC-7901 cell-cycle at S phase of cell division,increase the concentration of intracellular Ca2+ and decrease the expression of cyclinB1,the expressions of calcinerin and cytochrome-c were increased respectively.Conclusion Block of cell-cycle may be one of the mechanism of inducing cell apoptosis by D-glucosamine hydrochloride.

D-glucosamine hydrochloride(GAH) induce lymphocyte proliferation through Ca~(2+) signal pathway / 中国海洋药物

Objective To study the effect of GAH on lymphocytes proliferation and its mechanism. Methods MTT, fluorescence probe and immunofluorescent methods were used to investigate the effects of GAH on the lymphocytes proliferation, intracelluar Ca2+ concentration and expression of calcineurin(CaN). Results GHA induced lymphocyte proliferation, raised the intracelluar Ca2+ concentration and calcineurin expression. Conclusions GAH is a new kind of activator, which can induce lymphocyte proliferation through Ca2+ signal pathway.

Preliminary studies on the antitumor activities of D-glucosamine and its derivatives / 中国海洋药物

Objective The growth inhibitory effects of GlcNH_2?HCl,GlcNH_2 and NAG on human hepatoma SMMC-7721 cells in vitro was investigated.The antitumor activity of GlcNH_2?HCl against Sarcoma_(180) in KM mice was also investigated.Methods The cell viability in vitro was examined with MTT assay.DNA isolation and cell-cycle analyses were also performed.GlcNH_2?HCl was ig administered to Sarcoma_(180) KM mice.The inhibition rates,spleen and thymus index were calculated.Results GlcNH_2?HCl and GlcNH_2 resulted in a concentration-dependent reduction in hepatoma cell growth.The inhibition rates against SMMC-7721 cell of GlcNH_2?HCl and GlcNH_2 at concentration of 500?g?mL~(-1) were(50.24)% and 52.19%.As to the concentration of 1000?g?mL~(1), the rates were(82.21%) and 83.20%.This effect was accompanied by a marked increase in the proportion of S phase cells.Compared with the control,there was no significant difference among various concentrations of NAG,GlcNH_(2)?HCl exhibited inhibitiory effect against Sarcoma_(180) in mice at the dosage of 125～500 mg?kg~(-1),and the inhibition rate was about 27.84%～34.02%.The optimal inhibitory effect was 250 mg?kg~(-1).GlcNH_2?HCl could enhance the weights of thymus and spleen.In addition,it could promote lymphocyte transformation.Conclusion It is therefore postulated that the antitumor effect of GlcNH_2?HCl is probably host-mediated and cytocidal.

A STUDY ON CHITOSAN INHIBITING FIBROBLAST PROLIFERATION IN VITRO / 中国海洋药物

We use chitosan and n -acetyl -d -glucosamine to inhibit fibroblast proliferation which was cultured in vitro. The result shows that n - acetyl - d - glucosamine: ID50=16. 35mg/L, chitosan: ID50=69. 59mg/L. We also plant the chitosan membrane to the rabbit body to test its bio-degradation. The result shows that the molecular weight of chitosan drops 17% and 6% after 25 days and 18 days, respectively. On the basis of these results, we have obtained a conclusion that we can probably use chitosan to continuously release n-acetyl -d-glucosamine which can inhibit fibroblast proliferation effectively.