中国南海总合草苔虫抗癌活性成分研究(Ⅳ)Bryostatin 8,16的分离与结构鉴定

以体外抗癌活性为指标,采用多种层析分离技术,从采自广东大鹏湾海域的总合草苔虫中追踪分离得到8个活性单体.利用电喷雾离子质谱(ESI-MS)和高分辨(600MHz)核磁共振二维谱技术测定活性化合物的结构,分别鉴定为:bryostatin 4,bryostatin 5,bryostatin 6,bryostatin 8,bryostatin 10,bryostatin 11,bryostatin 16,bryostatin 18.其中,bryostatin 8(Ⅰ)和bryostatin 16(Ⅱ)是首次从南海总合草苔虫中获得,并在体外表现出显著的抗癌活性.     

中国南海总合草苔虫抗癌活性成分研究(IV)Bryostatin8,16的分离与结构鉴定

以体外抗癌活性为指标 ,采用多种层析分离技术 ,从采自广东大鹏湾海域的总合草苔虫中追踪分离得到 8个活性单体。利用电喷雾离子质谱 (ESI- MS)和高分辨 (60 0 MHz)核磁共振二维谱技术测定活性化合物的结构 ,分别鉴定为 :bryostatin 4 ,bryostatin 5 ,bryostatin 6,bryostatin 8,bryostatin 10 ,bryostatin 11,bryostatin16,bryostatin18。其中 ,bryostatin8( )和 bryostatin16( )是首次从南海总合草苔虫中获得 ,并在体外表现出显著的抗癌活性。     

中国南海总合草苔虫抗癌活性成分研究 Ⅲ Bryostatin 10, 11, 18的分离鉴定及其体外抗肿瘤活性

对采自广西北海的总合草苔虫进行抗癌活性成分的追踪分离,经溶媒提取和多种层析方法(Sephadex LH-20, ODS, HPLC等)分离,得到6个活性单体.利用电喷雾离子质谱(ESI-MS)和高分辨核磁共振(600 MHz)二维谱技术(DQF-COSY, HMQC, TOCSY, ROESY等),分别将其鉴定为:bryostatin 4, bryostatin 5, bryostatin 6,bryostatin 10,bryostatin 11,bryostatin 18.其中,bryostatin 10,bryostatin 11,bryostatin 18是首次从中国产总合草苔虫中获得,并在体外表现出显著的抗癌活性.     

中国南海总合草苔虫抗癌活性成分研究III Bryostatin10,11,18的分离鉴定及其体外抗肿瘤活性

对采自广西北海的总合草苔虫进行抗癌活性成分的追踪分离 ,经溶媒提取和多种层析方法 (SephadexL H- 2 0 ,ODS,HPL C等 )分离 ,得到 6个活性单体。利用电喷雾离子质谱 (ESI- MS)和高分辨核磁共振 (6 0 0MHz)二维谱技术 (DQF- COSY,HMQC,TOCSY,ROESY等 ) ,分别将其鉴定为 :bryostatin 4 ,bryostatin 5,bryostatin 6 ,bryostatin 10 ,bryostatin 11,bryostatin 18。其中 ,bryostatin 10 ,bryostatin 11,bryostatin 18是首次从中国产总合草苔虫中获得 ,并在体外表现出显著的抗癌活性。     

中国南海总合草苔虫中抗肿瘤活性成分研究——Ⅰ.Bryostatin 4～6的分离鉴定及其体外抗肿瘤活性

以中国南海海域大量生长的总合草苔虫为原料,将化学分离和活性追踪相结合,经溶媒提取和多种层析方法(Sephadex LH-20,ODS,HPLC等)分离,得到3个活性单体。采用高分辨核磁共振仪(600MHz)测定了它们的DQF-COSY、HMQC、TOCSY、NOESY、ROESY等二维相关谱。利用波谱解析和化学方法,分别将其鉴定为:bryostatin 4、bryostatin 5、bryostatin 6,并对其~1HNMR和~(13)CNMR数据做了订正。所有化合物均系首次从中国产总合草苔虫中获得,并在体外抗肿瘤活性筛选中都表现出显著的抗肿瘤活性。     

中国南海总合草苔虫抗癌活性成分研究：Ⅱ总草苔虫内酯的超强抗？…

目的 研究中国南海草苔虫中的大环内酯类抗癌活性成分,从中寻找高效的新型抗癌剂。方法 以体外抗癌活性为指标,将活性评价与化学分离相结合,采用凝胶柱层析（Ｓｅｐｈａｄｅｘ ＬＨ－２０）,反相硅胶快速柱层析（ＯＤＳ）和制备性高效液相层析等先进分离技术,对南中国海的总合草苔虫样本进行总活性成分的分离制备。采用ＭＴＴ法考察总活性成分对Ｋ５６２、Ｕ９３７肿瘤细胞株的体外抑制活性。结果 从该动物中分离制备了纯度     

中国南海总合草苔虫抗癌活性成分研究Ⅱ总草苔虫内酯的超强抗癌活性

目的：研究中国南海草苔虫中的大环内酯类抗癌活性成分,从中寻找高效的新型抗癌剂。方法：以体外抗癌活性为指标,将活性评价与化学分离相结合,采用凝胶柱层析（SephadexLH－20）,反相硅胶快速柱层析（CDS）和制备性高效液相层析等先进分离技术,对南中国海的总合草苔虫样本进行总活性成分的分离制备。采用MTT法考察总活性成分对K562、U937肿瘤细胞株的体外抑制活性。结果：从该动物中分离制备了纯度高达95％以上的总草苔虫内酯（bryostatins）,此总活性成分对红白细胞白血病细胞株K562具有超强的杀灭作用（ED50＜10－18μg／ml）,是天然产物中对K562肿瘤细胞抑制作用最强的化学成分。结论：我国南海总合草苔虫资源丰富,含有其独特的其超强抗癌活性的草苔虫内酯,为今后的新药研制与开发展示了美好前景。     

中国南海总合草苔虫中新的抗癌活性成分Bryostatinl9

自我国南海采集的总合草苔虫中,经多种层析方法分离到一种新的大环内酯化合物,应用化学方法和现代光谱技术(UV,IR,ESI-MS,~1HNMR,~(13)CNMR,2DNMR)确定了它的化学结构,并命名为bryo-statin19。体外抗癌活性试验表明,该化合物对U937单核细胞白血病细胞株有极强的杀灭作用,(ED_(50)=2.8×10~(-3)μg/ml),同时对HI-60早幼粒白血病和K562红白细胞白血病等细胞株均有显著的抑制作用。     

中国南海总合草苔虫抗癌活性成分研究ⅢBryostatin10,11,18的分 …

对采自广西北海的总合草苔虫进行抗癌活性成分的追踪分离,经溶媒提取和多种层析方法（ＳｅｐｈａｄｅｘＬＨ－２０,ＯＤＳ,ＨＰＬＣ等）分离,得到６个活性单体。利用电喷雾离子质谱（ＥＳＩ－ＭＳ）和高分辨核磁共振（６００ＭＨｚ）二维谱技术（ＤＱＦ－ＣＯＳＹ,ＨＭＱＣ,ＴＯＣＳＹ,ＲＯＥＳＹ等）,分别将其鉴定为：ｂｒｙｏｓｔａｔｉｎ４,ｂｒｙｏｓｔａｔｉｎ５,ｂｒｙｏｓｔａｔｉｎ６,ｂｒｙｏｓｔａｔｉｎ１０,     

总合草苔虫抗癌活性成分Bryostatins的研究概况

总合草苔虫Ｂｕｇｕｌａ ｎｅｒｉｔｉｎａ是一种海洋底栖动物，广泛分布于世界各海洋。自１９６８年美国亚利桑那州立大学癌研究所首次发现它的抗癌活性以来，以釜野德明为中心的Ｐｅｔｔｉｔ研究小组从中分离得到１８个大环内酯类化合物。     

Comparison of dexamethasone 8 mg and 16 mg for the prevention of acute and delayed cisplatin-induced emesis in patients with lung cancer

We performed a retrospective study that compared the efficacy and safety of dexamethasone (DEX) 8 mg with DEX 16 mg in cases of acute and delayed emesis induced by cisplatin (CDDP) chemotherapy in patients with lung cancer. Sixty-eight lung cancer patients treated with combination cisplatin, ifosfamide, and irinotecan therapy were studied. The DEX 8 mg group and the DEX 16 mg group received DEX intravenous injection 30 min prior to CDDP. All patients then received a 5-HT(3) antagonist intravenous injection 30 min before CDDP. Protection from acute nausea (day 1) was significantly superior in the DEX 16 mg group compared with the DEX 8 mg group (DEX 8 mg, 76.5%; DEX 16 mg, 100%). Protection from delayed emesis (day 1) was significantly superior in the DEX 16 mg group compared with the DEX 8 mg group. There was no reported severe nausea (grade 3) and vomiting (grade 2) in the DEX 16 mg group. Furthermore, perphenazine hydrochloride for use as rescue medication was required by significantly fewer patients in the DEX 16 mg group than in the DEX 8 mg group (DEX 8 mg, 41.2%; DEX 16 mg, 0%). Adverse effects were observed in 10 cases (nine reports of generalized fatigability, two of headache) in the DEX 8 mg group and in 16 cases (11 reports of generalized fatigability, one of pruritus) in the DEX 16 mg group. However, because the symptoms were all mild, we did not consider that there was any safety problem. In conclusion, DEX 16 mg is a clinically useful treatment for acute and delayed emesis induced by cisplatin-induced chemotherapy in patients with lung cancer.     

喹诺酮类药物与碳青霉烯类药物之间的交叉耐药性和泛耐药性的研究

目的研究由喹诺酮类和碳青霉烯类药物诱导的耐药性铜绿假单胞菌之间的交叉耐药,以及与庆大霉素(CN)、头孢哌酮/舒巴坦(SCF)之间的交叉耐药情况。方法用左氧氟沙星(LEV)和亚胺培南(IPM)分别诱导3株铜绿假单胞菌菌株(1株为标准菌株,2株为野生菌株),使之耐药,通过检测LEV、IPM、CN、SCF对该菌株的最低抑菌浓度(MIC),与未耐药菌株的MIC进行对比,观察药物间的交叉耐药情况。并通过对2005—2008年的铜绿假单胞菌耐药情况的分析,进一步观察上述药物间的交叉耐药情况。结果LEV、IPM、CN、SCF对由LEV诱导耐药的铜绿假单胞菌标准菌株的MIC值分别为32、16、16、32μg/ml,野生菌株的MIC值分别为16、8、8、64μg/ml和8、16、16、32μg/ml;LEV、IPM、CN、SCF对由LEV诱导耐药的铜绿假单胞菌标准菌株的MIC值分别为16、16、128、64μg/ml,野生菌株的MIC值分别为8、8、8、64μg/ml;和4、16、8、64μg/ml。结论由LEV、IPM诱导耐药的铜绿假单胞菌菌株,对LEV、IPM、CN、SCF均产生了不同程度的耐药性。提示喹诺酮类与碳青霉烯类药物的滥用都可能导致广泛的细菌交叉耐药。     

苯烷基异硫脲类化合物的合成及其一氧化氮合酶抑制活性苯烷基异硫脲类化合物的合成及其一氧化氮合酶抑制活性

目的寻找抑制神经型一氧化氮合酶(nNOS)并对痴呆症等有较好治疗作用的化合物。方法以异硫脲为母核,在其结构中引入苯烷基得到目的物,通过药物对神经细胞中亚硝酸盐含量的影响，测定目的物对nNOS的抑制作用。结果设计合成了16个新的苯烷基异硫脲类化合物(I1～16)。其结构经MS,IR,¹HNMR和元素分析确证。所有目的物均有不同程度的nNOS抑制活性，其中化合物I₈,I₁₂和I₁₄的活性较强。结论化合物I₈,I₁₂和I₁₄的活性强于阳性对照药S-甲基-N-(4-甲氧基苯基)异硫脲,IC₅₀达到1×10-7 mol·L^-1水平。     

Impact of surface derivatization of poly-L-lysine dendrimers with anionic arylsulfonate or succinate groups on intravenous pharmacokinetics and disposition

Tritium-labeled poly- l-lysine dendrimers displaying 8 or 16 surface lysines have been capped with benzene sulfonate (BS), benzene disulfonate (BDS), or succinate (Succ) groups, and the intravenous pharmacokinetics and disposition profiles of the resulting dendrimers (Lys(8)(BS)(16), Lys(16)(BS)(32), Lys(16)(BDS)(32), Lys(16)(Succ)(32)) have been evaluated. Lys(16)(Succ)(32) was rapidly removed from the plasma primarily via renal elimination. Lys(16)(BS)(32) and Lys(16)(BDS)(32) were opsonized, resulting in more prolonged plasma elimination kinetics and increased uptake by the liver. Data obtained at higher doses suggested some evidence of nonlinear pharmacokinetics. Lys(8)(BS)(16) had reduced affinity for plasma proteins and was cleared more rapidly than the larger Lys(16)(BS)(32) or Lys(16)(BDS)(32) dendrimers. Lys(8)(BS)(16) and Lys(16)(BS)(32) were metabolized in vivo, resulting in the production of a low molecular weight species (possibly the cleavage product Lys(BS) (2)) that was extensively renally eliminated and accounted for almost all of the radioactivity recovered in urine ( approximately 20-45% of administered (3)H). In contrast, only 3-5% of the administered (3)H was recovered in the urine of rats administered Lys(16)(BDS)(32), suggesting increased resistance to in vivo degradation. The plasma clearance, distribution, and metabolic profiles of lysine dendrimers are therefore significantly influenced by the structure and charge of the capping groups. In particular, larger arylsulfonate-capped lysine dendrimers are rapidly opsonized and initially cleared from the plasma by the reticuloendothelial organs. The degree of metabolism is subsequently dictated by the nature of the surface capping group with BDS surfaces seemingly more resistant to breakdown. In contrast, smaller arylsulfonate-capped dendrimers are less readily opsonized and phagocytozed but are metabolically labile, and succinate-capped dendrimers are rapidly eliminated by the kidneys.     

Effects of the phosphodiesterase 4 inhibitors SB 207499 and AWD 12-281 on the inflammatory reaction in a model of allergic dermatitis

The inhibitors of the phosphodiesterase 4, SB 207499 (cilomilast, c-4-cyano-4-(3-cyclopentyloxy-4-methoxy-phenyl)-r-L-cyclohexane carboxylic acid) and AWD 12-281 (N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide) were tested in a model of allergic dermatitis in mice. To obtain an allergic dermatitis, BALB/c mice were sensitized to toluene-2,4-diisocyanate. The allergic reaction was challenged by topical administration of toluene-2,4-diisocyanate onto the mice ears. Before challenge, two groups of mice were treated topically (ear skin) with SB 207499 or AWD 12-281. There was a significant ear swelling in toluene-2,4-diisocyanate-challenged mice ears 4, 8, 16, 24 and 48 h after challenge. SB 207499 and AWD 12-281 inhibited this swelling significantly 8, 16, 24 and 48 h after the challenge. For biochemical parameters and histology, ears were sampled from mice sacrificed 4, 8 and 16 h after the challenge. In homogenized tissue, SB 207499 and AWD 12-281 inhibited significantly the secretion of interleukin 1beta induced by toluene-2,4-diisocyanate 4 and 8 h after challenge. The cell influx (granulocytes) observed in the toluene-2,4-diisocyanate-challenged mice 8 and 16 h after challenge was nearly abolished by AWD 12-281 and SB 204799.     

Regulation by growth hormone and glucocorticoid of testosterone metabolism in long-term cultures of hepatocytes from male and female rats.

The activities of 2-, 6 beta-, 7 alpha- and 16 alpha-testosterone hydroxylase and 5 alpha-testosterone reductase were measured in intact hepatocytes from male and female rats cultured for 8 days in a modified Waymouth medium supplemented with 0.1 or 1.0 microM dexamethasone with or without addition of 1 microgram/mL growth hormone. During culture of hepatocytes from female rats the activity of the male-specific 16 alpha-testosterone hydroxylase increased. This increase was significantly inhibited at day 8 by 1 microM dexamethasone as well as by growth hormone. Furthermore, in cultures of hepatocytes from male rats, the activity of the constitutive 16 alpha-testosterone hydroxylase was decreased by 1 microM dexamethasone as well as by growth hormone. The induction of 6 beta-testosterone hydroxylase by dexamethasone was suppressed by growth hormone in hepatocytes from both male and female rats, while the 7 alpha-testosterone hydroxylase activity was unaffected by culture time, hormone additions and gender. The decrease in female-specific 5 alpha-reductase activity with culture time in hepatocytes from female rats was significantly attenuated by growth hormone at 0.1 microM dexamethasone. The effects of growth hormone on testosterone hydroxylase activities in hepatocyte cultures from male and female rats are in accordance with the concept of growth hormone as a "feminization signal". The results suggest that the glucocorticoid-dependent expression of the male constitutive 16 alpha-hydroxylase requires periods of low levels of growth hormone.     

Protective effects of m-nisoldipine and nisoldipine on myocardial damage in working rabbit hearts after ischemia-reperfusion

m-Nisoldipine 4, 8, 16 nmol/L, nisoldipine 1, 4 nmol/L and nifedipine 4, 8, 16, 50 nmol/L enhanced the recoveries of functional parameters of working rabbit hearts after ischemia-reperfusion, as well as prevented the development of contracture and the release of CPK from the reperfused hearts. m-Nisoldipine 8 nmol/L, nisoldipine 1 nmol/L and nifedipine 8 nmol/L attenuated the reduction of myocardial Na+-K+-ATPase and 5'-nucleotidase activity induced by ischemia-reperfusion. The breakdown of membrane phospholipids and elevation of the myocardial Ca2+-ATPase activity and the free fatty acids level were also prevented.     

Poriacosones A and B: two new lanostane triterpenoids from Poria cocos

Two new lanostane triterpenoids, poriacosones A (8) and B (9), together with eight known compounds were isolated from the sclerotia of Poria cocos (Schw.) Wolf (Polyporaceae), and identified by spectroscopic analysis, including IR, UV, CD, ESI-TOF-MS, HR-SIMS, 1D-, and 2D-NMR spectra. The structures of the new compounds were established as 3alpha,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (8) and 3beta,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (9).     

Poriacosones A and B: two new lanostane triterpenoids from Poria cocos

Two new lanostane triterpenoids, poriacosones A (8) and B (9), together with eight known compounds were isolated from the sclerotia of Poria cocos (Schw.) Wolf (Polyporaceae), and identified by spectroscopic analysis, including IR, UV, CD, ESI-TOF-MS, HR-SIMS, 1D-, and 2D-NMR spectra. The structures of the new compounds were established as 3alpha,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (8) and 3beta,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (9).