Synthesis and cytotoxic evaluation of novel ester-triazole-linked triterpenoid–AZT conjugates

Betulinic acid and analogous naturally occurring triterpenoid acids were transformed into the corresponding propargyl esters and subsequently deployed as substrates for a click chemistry-mediated coupling with azidothymidine (AZT) en route to novel 1,2,3-triazole-tethered triterpenoid–AZT conjugates. Twelve new hybrids were thus prepared and assessed in terms of their cytotoxic activity, revealing an interesting anticancer activity of five triterpenoid–AZT hybrids on KB and Hep-G2 tumor cell lines.     

Phytochemical and cytotoxic studies on the roots of Euphorbia fischeriana

With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1–3) and six known ones (4–9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC₅₀ 8.1 μmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC₅₀ values of 12.5, 12.0 and 18.7 μmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC₅₀ 11.9 μmol/L) and 8 (IC₅₀ 9.4 μmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC₅₀ values of 28.2 and 29.8 μmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects.     

灵芝子实体中的羊毛脂烷型灵芝酸酯类成分研究

目的 系统研究灵芝子实体中的羊毛脂烷型灵芝酸酯类成分。方法 通过氯仿对盐酸酸化的灵芝子实体提取物中的羊毛脂烷型三萜酸类成分进行萃取,结合硅胶柱层析、中压柱层析（RP C18色谱柱）、制备型HPLC（RP C18色谱柱）对提取物中的三萜酸酯类化学成分进行系统的分离、纯化。通过UV、ESI-MS、HRESI-MS、1H-NMR、13C-NMR、HSQC、HMBC、NOESY等波谱学手段结合文献数据对制备得到的三萜类单体成分进行准确的结构测定。结果 从灵芝子实体的氯仿提取物中共分离鉴定了10个羊毛脂烷型灵芝酸酯类成分,分别为：（1）Ganoderic acid AP,（2）Methyl Ganoderate G,（3）Ganoderic acid H,（4）12-Hydroxy-3,7,11,15,23-pentaoxo-5-lanost-8-en-26-oic acid,（5）Ganoderic acid K,（6）Ganoderenic acid B,（7）Lucienic acid A,（8）Lucidenic acid B,（9）20（21）-Dehydrolucidenic acid A,（10）Lucidone D。结论 灵芝子实体中极性较小的化学成分主要为羊毛脂烷型三萜及其降碳衍生物,该类成分多具有羧基或羧酸酯官能团,既而也称灵芝酸类,本文共分离鉴定了10个该系列成分,其中化合物1为新化合物。     

On immunotherapies and cancer vaccination protocols: A mathematical modelling approach

In this paper we develop a new mathematical model of immunotherapy and cancer vaccination, focusing on the role of antigen presentation and co-stimulatory signaling pathways in cancer immunology. We investigate the effect of different cancer vaccination protocols on the well-documented phenomena of cancer dormancy and recurrence, and we provide a possible explanation of why adoptive (i.e. passive) immunotherapy protocols can sometimes actually promote tumour growth instead of inhibiting it (a phenomenon called immunostimulation), as opposed to active vaccination protocols based on tumour-antigen pulsed dendritic cells. Significantly, the results of our computational simulations suggest that elevated numbers of professional antigen presenting cells correlate well with prolonged time periods of cancer dormancy.     

Significance of inoculation density control in production of polysaccharide and ganoderic acid by submerged culture of Ganoderma lucidum

Control of inoculation density was significant for cell growth, morphology, and production of polysaccharide and ganoderic acid in submerged culture of the higher fungus Ganoderma lucidum. A maximal cell concentration of 15.7 g dry cell weight (DW)/l was obtained at an inoculation density of 330 mg DW/l. For inoculation density within the range of 70–670 mg DW/l, a large inoculation density led to a small pellet size and high production of extracellular and intracellular polysaccharides, while a relatively big pellet size and high accumulation of ganoderic acid were observed at a low inoculation density. It was also shown that small pellet size resulted in high polysaccharide production, while large pellet size led to high production of ganoderic acid.     

变转速策略调控灵芝菌丝体发酵高产三萜

灵芝发酵过程中,采用变转速调控策略,对振荡发酵阶段进行优化,以期达到高产三萜的目的。振荡阶段最佳条件为转速由150r/min变为100r/min,该策略与液体静置培养相结合,最终菌丝体三萜产量高达678.0g/L,比优化前提高了21%。振荡发酵阶段的变转速策略有效地提高了三萜的产量。     

灵芝发酵菌丝体中灵芝酸的分离纯化及生物活性检测

灵芝深层发酵菌丝体经甲醇提取得到粗灵芝酸,以甲苯:乙酸乙酯:乙酸(12:4:0.5)为展开剂,通过硅胶薄层层析法分离得到三种灵芝酸,命名为M_1,M_2和M_3,其R_f值分别为0.56,0.49,0.17.在优化的硅胶柱层析条件下,即以CH_3OH:CHCl_3=3:97,5:95,1:9为洗脱剂,进行分段洗脱;进样量:硅胶量=1:60;在30m×500mm的层析柱上纯化得到三种灵芝酸.抗菌实验显示,三种四环三萜酸具有抑制大肠杆菌、产气杆菌、肠炎杆菌、金黄色葡萄球菌和枯草芽孢杆菌生长的活性.     

Borrelidins F–I,cytotoxic and cell migration inhibiting agents from mangrove-derived Streptomyces rochei SCSIO ZJ89

Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from Streptomyces rochei SCSIO ZJ89 originating from a mangrove-derived sediment sample. These structurally diverse metabolites enabled a number of new structure-activity relationships (SARs) to be identified, especially with respect to the different configurations at the C11-OH and C12–C15 double bonds for which the absolute configurations were determined using spectroscopic methods. Importantly, borrelidin H (4) was found to have a therapeutic window superior to that of borrelidin A (1) in vitro and could inhibit migration of cancer cells.