紫杉烷二萜类化合物精细立体结构研究

抗肿瘤药物紫杉醇(taxol)是一类新型的纺锤体毒药物。已有的关于紫杉醇及其类似物的构效关系研究表明其分子结构中六元A环的C-13侧链与C₄-C₅-C₂₀四元氧环对活性有重要贡献。本文研究了紫杉烷二萜类化合物中5/7/6三环骨架C-4取代方式不同的化合物(4个)及6/8/6三环骨架C-4取代方式不同的3类化合物(10个)的晶体结构,阐述了晶态下紫杉烷二萜类化合物因C-4取代方式不同对分子立体结构的影响,从晶体学角度给出6/8/6/4骨架与抗癌活性的关系。     

Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the IC₅₀ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.     

Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents

From the n-hexane fraction of the fruits of Vitex agnus-castus, two labdane-type diterpenes, vitetrifolin B and C, were isolated by means of multiple chromatographic separations, together with the previously identified rotundifuran, vitexilactone and the sesquiterpene spathulenol. From the EtOAc fraction, eupatorin was identified for the first time, besides the known casticin, penduletin, vitexin and orientin. The n-hexane, EtOAc and MeOH-H(2)O fractions of the MeOH extract of Agni-casti fructus were subjected to in vitro antioxidant assays. The EtOAc extract displayed a significant concentration-dependent effect when tested by 1,1-diphenyl-2-picrylhydrasyl (DPPH) free radical assay (IC(50) = 68 microg/mL) and against the autooxidation of a standard rat brain homogenate (IC(50) = 14 microg/mL). The MeOH-H(2)O fraction was less active with 3643 microg/mL (DPPH test) and IC(50) = 125 microg/mL (rat brain homogenate), while the n-hexane phase proved to be inactive. The main flavonoid constituents of the EtOAc extract, casticin, vitexin and orientin were assayed for antioxidant activity and found that only casticin possesses a marked lipid peroxidation inhibitory effect (IC(50) = 0.049 mm) compared with that of the positive control ascorbic acid (IC(50) = 0.703 mm).     

Experimental antihyperglycemic effect of diterpenoids of llareta Azorella compacta (Umbelliferae) Phil in rats

Aqueous or ethanol infusions of Azorella compacta (llareta) in common with many other plants have been used as antidiabetic in the popular medicine in the altiplanic region of Chile. In order to determine if the diterpenic compounds chemically elucidated and isolated from this plant are responsible for this effect, streptozotocin diabetic rats (507 +/- 67 mg/mL glucose) were injected with two injections of diterpenic compounds mulinolic acid, azorellanol, and mulin-11,13-dien-20-oic acid at 180 mg/mL. Glycemia of animals treated with mulinolic acid and azorellanol was decreased to 243 +/- 2 and 247 +/- 14 mg/mL respectively, values very close to those reached by chlorpropamide injection used in controls. After 3 h treatment with mulin-11,13-dien-20-oic acid no effect was detected. The blood serum insulin in diabetic rats (146 +/- 58 pg/mL) was lower than in control rats. After injection of azorellanol, insulin was elevated to 247 +/- 23 pg/mL but with mulinolic acid, insulin was not changed. The antihyperglycemic effect of these compounds may explain the effectiveness of llareta in popular medicine. Because of the similarity to the hypoglycemic medication chlorpropamide, azorellanol could be acting on the beta cells of pancreatic islets, while mulinolic acid may act upon glucose utilization or production in the liver.     

毛梗豨莶化学成分的研究Ⅰ

 目的：对毛梗莶(Siegesbeckia glabrescens Makino.)地上部分的化学成分进行分离，并鉴定其化学结构。方法：采用柱层色谱法进行分离，从中分离到6个化合物，用IR,MS，¹HNMR，¹³CNMR和²DNMR等光谱技术鉴定化合物的结构。结果：经光谱鉴定化合物为：化合物Ⅰ大花酸(grandifloric acid)，化合物Ⅱ16β，17-二羟基 贝壳杉烷(16β,17-dihydroxy-kaurane)，化合物Ⅲ阿魏酸(ferulic acid)，化合物Ⅳ二十七烷醇(heptacosanol)，化合物(Ⅴ)β-谷甾醇(β－sitosterol)，化合物Ⅵ琥珀酸(sucinicacid)。结论：化合物(Ⅰ)，(Ⅱ)为kaurane型二萜类化合物，化合物(Ⅲ)、(Ⅳ)、(Ⅵ)为首次从该植物中分离得到。     

云南红豆杉化学成分研究

从云南红豆杉的树皮中分离得到4个紫杉烷类二萜化合物及1个黄烷醇类化合物。根据理化常数及光谱分析确定为紫杉醇C-7-木糖甙,紫杉醇B,10-去乙酰基巴卡亭Ⅲ,紫杉素及2R,3R-儿茶精。     

Glabcensin Q-U, five new ent-kaurane diterpenoids from Isodon angustifolius var. glabrescens

Examination of the diterpenoid constituents of the dried leaves of Isodon angustifolius var. glabrescens led to the isolation of five new ent-kaurane diterpenoids, named as glabcensin Q-U (2-6). The structures were elucidated on the basis of spectroscopic evidences.     

臭牡丹的化学成分研究

研究臭牡丹Clerodendrum bungei的化学成分。采用硅胶,Sephadex LH-20,MCI,ODS和半制备HPLC等色谱技术,从臭牡丹95%乙醇提取物中分离得到10个化合物,分别鉴定为11,12,16S-trihydroxy-7-oxo-17(15→16),18(4→3)-diabeo-abieta-3,8,11,13-tetraen-18-oic acid(1),12 S*,13R*-dihydroxy-9-oxo-octadeca-10(E)-enoic acid(2),赪桐苷A(3),trichotomoside(4),山橘脂酸(5),4'-O-methylscutellarein(6),neroplomacrol(7),butylitaconic acid(8),hexylitaconic acid(9),对羟基苯甲酸(10)。化合物1和2为新天然产物,化合物7~10为首次从该属植物中分离得到,化合物为3,5,6首次从该植物中分离得到。     

Three new compounds from Cinnamomum cassia

Three new compounds, including two new diterpenoids, named epianhydrocinnzeylanol (1) and cinnacasiol H (2), and one hydroxylasiodiplodin, (3R,4S,6R)-4,6-dihydroxy-de-O-methyllasiodiplodin (3), together with five known diterpenoids (4–8) and two known phenolic glycosides (9–10) were isolated from the barks of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic analysis and comparison of the chemical shift values with those of related known compounds. The anti-inflammatory activities of the isolates were evaluated on nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells and the compounds showed weak inhibition activities.     

Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata

The present study was carried out to evaluate anti‐Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC₅₀, 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti‐H. pylori agents possessing urease inhibition. Copyright © 2015 John Wiley & Sons, Ltd.