UV-Guided isolation of alantrypinone, a novel Penicillium alkaloid

Fumiquinazoline F (1) and alantrypinone (2) have been isolated as the two major metabolites of Penicillium thymicola. The structure of 2, which contains a new ring structure, was elucidated by analysis of spectroscopic data including 2D NMR. The absolute configuration of 2 was established by a single-crystal X-ray diffraction study.     

Mechanism of action cryptophycin. Interaction with the Vinca alkaloid domain of tubulin

Cryptophycin is a potent antitumor agent that depletes microtubules in intact cells, including cells with the multidrug resistance phenotype. To determine the mechanism of action of cryptophycin, its effects on tubulin function in vitro were analyzed. Cryptophycin reduced the in vitro polymerization of bovine brain microtubules by 50% at a drug:tubulin ratio of 0.1. Cryptophycin did not alter the critical concentration of tubulin required for polymerization, but instead caused substoichiometric reductions in the amount of tubulin that was competent for assembly. Consistent with its persistent effects on intact cells, cryptophycin-treated microtubule protein remained polymerization-defective even after cryptophycin was reduced to sub-inhibitory concentrations. The effects of cryptophycin were not due to denaturation of tubulin and were associated with the accumulation of rings of microtubule protein. The site of cryptophycin interaction with tubulin was examined using functional and competitive binding assays. Cryptophycin blocked the formation of vinblastine-tubulin paracrystals in intact cells and suppressed vinblastine-induced tubulin aggregation in vitro. Cryptophycin inhibited the binding of [3H]vinblastine and the hydrolysis of [gamma32P]GTP by isolated tubulin, but did not block the binding of colchicine. These results indicate that cryptophycin disrupts the Vinca alkaloid site of tubulin; however, the molecular details of this interaction are distinct from those of other antimitotic drugs.     

Martefragin A, a novel indole alkaloid isolated from red alga, inhibits lipid peroxidation

Martefragin A (1), a novel indole alkaloid, was isolated from a red alga, Martensia fragilis, by repeated column chromatography. The structure of 1 was elucidated on the basis of spectral analysis of its methyl ester (2), including 1H- and 13C-NMR, 1H-1H correlation spectroscopy (COSY), and 13C-1H COSY. A single crystal X-ray analysis of the hydrochloride of 1 confirmed the assignment. Martefragin A (1) showed inhibitory activity on NADPH-dependent lipid peroxidation in rat liver microsomes. The IC50 values of 1, alpha-tocopherol and ascorbic acid were 2.8, 87 and 200 microM, respectively.     

Korundamine A, a novel HIV-inhibitory and antimalarial "hybrid" naphthylisoquinoline alkaloid heterodimer from Ancistrocladus korupensis

A unique heterodimeric naphthylisoquinoline alkaloid, korundamine A (2), comprised of two different monomeric biaryl halves, has been isolated from the Cameroonian tropical liana Ancistrocladus korupensis. Korundamine A is the first "hybrid" dimer found in the Ancistrocladaceae; in vitro, it demonstrated anticytopathic activity against HIV-1 and antimalarial activity against Plasmodium falciparum.     

一类含氟希夫碱液晶的合成及中间相性能

合成了一系列希夫碱酯类化合物——4-(4-烷基反式环己基)苯甲酸4-(2,3,4-三氟苯胺亚甲基)苯酚酯.通过红外光谱(FTIR)和氢核磁共振(¹H NMR)对产物化学结构进行了确认,并采用偏光显微镜(POM)和差示扫描量热仪(DSC)对其中间相性能进行了研究.结果表明,所得产物均存在近晶相和向列相且清亮点均高于300℃;随着烷基链长度增加,其熔点降低,但对清亮点的影响不大,近晶相存在的温度范围增大,而向列相温度范围缩小.     

Poisoning the spindle: serendipity and discovery of the anti-tumor properties of the Vinca alkaloids

In 1995, Canadian scientists Robert Noble and Charles Beer were inducted into the Canadian Medical Hall of Fame for their 1950s "discovery" of Vinblastine. Their "chance" finding of an anticancer drug in the leaves of the periwinkle plant (Vinca rosea, Linn.), is used to explore the historical issue of discovery, accidental discovery, and priority. The elements of the discovery are reconstructed through the oral testimony of key players and their published and unpublished records. Several "unsung heroes" played key roles in this project and reasons for their relative invisibility will be presented. Special attention is paid to the relationship between the small Canadian academic group working at UWO and the large pharmaceutical company (Eli Lilly) engaged in similar research at the same time.     

Synthesis of novel fluorinated coumarins: excellent UV-light excitable fluorescent dyes

Two new fluorinated fluorescent dyes, 6,8-difluoro-7-hydroxy-4-methylcoumarin (Marina Blue) and 3-carboxy-6,8-difluoro-7-hydroxycoumarin (Pacific Blue), exhibit excellent photophysical properties among a series of novel fluorinated 7-hydroxycoumarins. Most of these fluorinated coumarins have quantum yields (0.63 to 0.89) equal to or higher than that of the parent compound (0.63), which, in combination with their lower pKaS and higher photostability, make them superior fluorescent dyes for use as reporter molecules in biological systems.     

Cell surface binding and cellular internalization properties of suramin, a novel antineoplastic agent

BACKGROUND: A number of factors contribute to increased risk of coronary heart disease (CHD) among postmenopausal women, including atherogenic changes in serum cholesterol profiles, weight gain, and decreases in physical activity during the menopause. To date, no study has attempted to prevent elevations in primary CHD risk factors as women experience menopause. METHODS: A sample of 535 healthy premenopausal women, ages 44-50, were recruited for an ongoing 5-year randomized prevention trial testing whether increases in low-density lipoprotein cholesterol (LDL-C) and body weight can be prevented during the menopause with a dietary and behavioral intervention. The aim was to reduce total dietary and saturated fat and cholesterol, prevent weight gain, and increase physical activity levels. Changes in CHD risk factors after the first 6 months of treatment were analyzed comparing 253 intervention and 267 assessment-only control participants. RESULTS: The intervention group showed significant reductions in total cholesterol (-0.34 mmol/liter), LDL-C (-0.28 mmol/liter), triglycerides (-0.04 mmol/liter), weight (-4.8 kg), waist-hip ratio (-0.008), systolic blood pressure (-3.5 mm Hg), diastolic blood pressure (-2.2 mm Hg), serum glucose levels (-0.06 mmol/liter), and HDL-C (-0.06 mmol/liter) and significant increases in physical activity (+383 kcal). No significant changes were observed in the control group. CONCLUSION: Six-month results suggested that participants were receptive to the preventive approach to CHD risk reduction and were successful in making initial positive lifestyle changes. Follow-up data will evaluate long-term adherence to the intervention and the interaction between adherence and physiological changes during menopause.     

Photochemistry and photophysical properties of novel, unsymmetrically substituted metallophthalocyanines

In order to gain insight into the relation between health and people's environment, literature published between 1985 and 1994 was gathered from several international databases. An introduction into existing theory regarding geographic disparities is presented: geographical drift and breeder hypotheses are discussed. This is followed by a critical review focusing on interaction effects of urbanicity and individual characteristics on health. This leads to two major conclusions. First, emphasis in past research has been primarily on urban constraints rather than opportunities. Positive aspects of urban living are often insufficiently appreciated. Second, positive and negative environmental aspects have an effect on health that is often dependent on individual characteristics. The extent to which the environment exerts influence on a person's health is dependent on that person's individual characteristics. These conclusions are relevant only for further developing the breeder hypothesis, however. Large scale individual based longitudinal data should be studied in order to gain more insight into the relative importance of the geographical drift hypothesis.     

Synthesis,characterization and fluorescence properties of a novel rare earth complex for anti-counterfeiting material

A novel ligand with two ester groups, two benzene rings and two carboxyl groups was synthesized. The composition and structure of the ligand were characterized by the Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectrum (NMR) and UV spectrometer. The rare-earth complex with the ligand and 1, 10-phenanthroline (phen) was synthesized and structurally characterized by FT-IR, TG and fluorescent spectrometer. The results showed that the novel multicarboxyl ligand could efficiently transfer the energy to Eu³⁺ ions in the complex and sensitize the luminescence of the rare earth ions, and the complex could emit strong fluorescence of the rare earth ions.     

Synthesis,characterization and fluorescence properties of a novel rare earth complex for anti-counterfeiting material

A novel ligand with two ester groups,two benzene rings and two carbox yl groups was synthesized. The composition and structure of the ligand were char acterized by the Fourier transform infrared spectroscopy(FT-IR) ,nuclear magnet ic resonance spectrum(NMR) and UV spectrometer. The rare-earth complex with the ligand and 1,10-phenanthroline(phen) was synthesized and structurally charact erized by FT-IR,TG and fluorescent spectrometer. The results showed that the no vel multicarboxyl ligand could efficiently transfer the energy to Eu3+ ions in t he complex and sensitize the luminescence of the rare earth ions,and the comple x could emit strong fluorescence of the rare earth ions.     

Synthesis,characterization and fluorescence properties of a novel rare earth complexes with a multi-branched ligand and 1, 10-phen

A novel multi-branched ligand with multiple ester groups, multiple benzene rings and multiple carboxyls was synthesized. The composition and structure of the ligand were characterized through the Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectrum (¹H NMR) and UV spectrometer. The composition and fluorescence properties of rare earth complexes with the ligand and 1,10-phenanthroline (phen) were researched via FT-IR, EA and fluorescent spectrometer. The results presented that the resulting complex had strong characteristic fluorescence spectrum of the rare earth ions, which was attributed to the synergistic effects of the ligand, phen, and rare earth ion.     

Synthesis,characterization and fluorescence properties of a novel rare earth complexes with a multi-branched ligand and 1,10-phen

A novel multi-branched ligand with multiple ester groups,multiple benzene rings and multiple carboxyls was synthesized.The composition and structure of the ligand were characterized through the Fourier transform infrared spectroscopy(FT-IR),nuclear magnetic resonance spectrum(1H NMR) and UV spectrometer.The composition and fluorescence properties of rare earth complexes with the ligand and 1,10-phenanthroline(phen) were researched via FT-IR,EA and fluorescent spectrometer.The results presented that the resulting complex had strong characteristic fluorescence spectrum of the rare earth ions,which was attributed to the synergistic effects of the ligand,phen,and rare earth ion.     

Development of novel 19F NMR pH indicators: synthesis and evaluation of a series of fluorinated vitamin B6 analogues

Phytochemicals such as indole-3-carbinol (I3C) and sulforaphane are components of cruciferous vegetables which exhibit antitumorigenic activity associated with altered carcinogen metabolism and detoxification. Diindolylmethane (DIM) is a major acid-catalyzed metabolite of I3C formed in the gut that binds to the aryl hydrocarbon receptor (AhR) and treatment of MCF-7 human breast cancer cells with 10-50 microM DIM resulted in rapid formation of the nuclear AhR complex and induction of CYP1A1 gene expression was observed at concentrations >50 microM. Previous studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high affinity AhR ligand, inhibits 17beta-estradiol (E2)-induced responses in MCF-7 cells and growth of E2-dependent 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Results of this study show that like TCDD, DIM inhibits E2-induced proliferation of MCF-7 cells, reporter gene activity in cells transiently transfected with an E2-responsive plasmid (containing a frog vitellogenin A2 gene promoter insert) and down-regulates the nuclear estrogen receptor. Moreover, DIM (5 mg/kg every other day) also inhibits DMBA-induced mammary tumor growth in Sprague-Dawley rats and this was not accompanied by induction of hepatic CYP1A1-dependent activity. Thus, DIM represents a new class of relatively non-toxic AhR-based antiestrogens that inhibit E2-dependent tumor growth in rodents and current studies are focused on development of analogs for clinical treatment of breast cancer.     

Stellettamide B, a new indolizidine alkaloid from a sponge of the genus Stelletta

BACKGROUND: The availability of nasal mask bi-level positive airway pressure (BiPAP) support in managing respiratory failure following cardiovascular surgery was studied. MATERIALS AND METHODS: BiPAP support was used for eight patients requiring postoperative prolonged respiratory support of 72 hours or longer. Their mean age was 65 years of age and the mean periods of postoperative endotracheal intubation was 12+/-5 days. BiPAP support was removed within 48 hours in six out of eight patients. Reintubation of an endotracheal tube was not necessary in all eight patients after the BiPAP treatment. RESULTS: The respiratory rates during the BiPAP management remained unchanged. The values of the respiratory index significantly (p<0.01) improved after BiPAP management (1.5+/-0.2 --> 0.9+/-0.2). A-aDO2 and Qs/Qt decreased (p<0.1) after the BiPAP management. There were no significant differences in central venous pressure and circulatory states during BiPAP support. CONCLUSIONS: In conclusions, BiPAP support is a noninvasive management technique for postoperative respiratory failure and may also prevent prolonged endotracheal intubation.