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  • 1
    ISSN: 1520-6025
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1520-6025
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-203X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Cell suspension cultures, derived from roots of Podophyllum hexandrum Royle (Berberidaceae), accumulate podophyllotoxin. In this study the use of β-cyclodextrin in feeding the poorly water-soluble precursor coniferyl alcohol to these cultures is described. By complexation with β-cyclodextrin, a solution of 3 mM coniferyl alcohol could be fed, resulting in enhanced podophyllotoxin accumulation. The same concentration of non-complexed suspended coniferyl alcohol had only little effect on the podophyllotoxin accumulation. β-Cyclodextrin itself was proven to be non-toxic for the cells. It did not influence the podophyllotoxin content and it was not metabolized or used as a carbon source by the cells. For comparison, coniferin, the water-soluble β-D-glucoside of coniferyl alcohol, was also fed in the same concentration. The effect of coniferin on the podophyllotoxin accumulation was stronger than that of coniferyl alcohol complexed with β-cyclodextrin, but coniferin is not commercially available.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-739X
    Keywords: Cells, cultured ; Levodopa ; Mucuna pruriens ; Selection (genetics)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Routinely grown cell suspension cultures ofMucuna pruriens L. (Fabaceae) were able to endogenously accumulate the anti-Parkinson drug L-dihydroxyphenylalanine (L-dopa) in the range between 0.2 and 2% on a dry weight (DW) basis. The green colour that developed in light-exposed cultures, appeared to be a suitable marker to select cells with an increased L-dopa biosynthesis and/or phenoloxidase activity. For this purpose, saccharose concentrations from 0 to 4% (w/v), and light intensities of 1,000 and 2,000 lux, were involved in the selection procedure. After 6 months, photomixotrophic callus cultures with a rapid growth and a high L-dopa content of 0.9% (DW) were obtained on 2% saccharose and under 1,000 lux. The cell suspensions, derived from these calli, accumulated up to 6% (DW) L-dopa, which was the highest stable content ever measured in cultures ofM. pruriens. An L-dopa yield of approximately 1.2 g/l was calculated after 6 days of growth. In contrast, compared with the standard-grown parent cell line, the phenoloxidase activity, and consequently the bioconversion capacity as measured after entrapment in calcium alginate, of these high-producing cultures was approximately threefold lower.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-739X
    Keywords: Antimalarials ; Artemisia annua L ; Artemisinin ; Biosynthesis ; Chemistry ; Clinical trials ; Pharmacology ; Phytochemistry ; Sesquiterpenes ; Toxicology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Artemisinin, a sesquiterpene lactone endoperoxide isolated fromArtemisia annua L., and a number of its semisynthetic derivatives have shown to possess antimalarial properties. They are all eflective againstPlasmodium parasites that are resistant to the newest and commonly used antimalarial drugs. This article gives a survey of the literature dealing with artemisinin-relaled antimalarial issues that have appeared from the end of 1989 up to the beginning of 1994. A broad range of medical and pharmaceutical disciplines is covered, including phytochemical aspects like the selection of high-producing plants, analytical procedures, and plant biotechnology. Furthermore, the organic synthesis of artemisinin derivatives is discussed, as well as their mechanism of action and antimalarial activity, metabolism and pharmacokinetics, clinical studies, sideeffects and toxicology, and biological activities other than antimalarial activity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-5044
    Keywords: antimalarial drugs ; Artemisa annua ; artemisinin ; sesquiterpene lactones ; shoot culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract From aseptically grown Artemisia annua plantlets, shoot cultures were initiated. Using different concentrations of auxine, cytokinine and sucrose, a suitable culture medium was developed, with respect to the growth of the shoots and their artemisinin accumulation. Nitrate concentration and conductivity appeared to be suitable growth parameters. The artemisinin content was measured gas chromatographically. The shoot cultures were maintained in the developed standard medium, consisting of a half concentration of MS-salts with vitamins, 0.2 mg l-1 BAP, 0.05 mg l-1 NAA and 1% sucrose. The growth of the shoots and the artemisinin content remained stable for a longer period. They showed considerable photosynthetic activity and generally contained ca. 0.08% artemisinin on a dry weight basis. The highest artemisinin content found was 0.16% in the above mentioned standard medium, but also on the same medium with 0.5% sucrose. Attempts were made to further improve the artemisinin production by varying the medium composition through addition of gibberellic acid or casein hydroly-state; by omitting plant growth regulators; by precursor feeding, i.e. mevalonic acid; by influencing the biosynthesis routing through inhibition of the sterol synthesis by miconazole, naftifine or terbinafine; by changing gene expression with 5-azacytidine or colchicine; and by elicitation, using cellulase, chitosan, glutathione or nigeran. Enhanced artemisinin production was found with 10 mg l-1 gibberellic acid, 0.5 g l-1 casein hydrolysate, 10 mg l-1 or 20 mg l-1 naftifine. Relative increases of 154%, 169%, 140% and 120% were found, respectively. Other additions caused the growth to cease and the artemisinin contents to drop.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Plant cell, tissue and organ culture 38 (1994), S. 103-113 
    ISSN: 1573-5044
    Keywords: Bioconversion ; catechols ; cyclodextrins ; lignans ; plant cell cultures ; solubility enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The application of cyclodextrins as precursor solubilizers in biotechnological processes, in which plant cells are involved, is new. In this paper the possibilities for cyclodextrin facilitated bioconversions by freely suspended and/or immobilized plant cells or plant enzymes are demonstrated. After complexation with β-cyclodextrin, the phenolic steroid 17β-estradiol could be ortho-hydroxylated into a catechol, mainly 4-hydroxyestradiol, by a phenoloxidase from in vitro grown cells of Mucuna pruriens. By complexation with β-cyclodextrin the solubility of the steroid increased from almost insoluble to 660 μM. In addition, by complexation with β-cyclodextrin, a solution of 3 mM coniferyl alcohol could be fed to cell cultures of Podophyllum hexandrum in order to enhance the accumulation of podophyllotoxin. Finally, the glucosylation of podophyllotoxin by cell cultures derived from Linum flavum was investigated. Four cyclodextrins: β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin and dimethyl-β-cyclodextrin were used to improve the solubility of podophyllotoxin. Dimethyl-β-cyclodextrin met our needs the best and the solubility of podophyllotoxin could be enhanced from 0.15 to 1.92 mM. Podophyllotoxin-β-d-glucoside was formed at a rate of 0.51 mmol l-1 suspension per day by the L. flavum cells growing in the presence of 1.35 mM podophyllotoxin, complexed with dimethyl-β-cyclodextrin.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-5044
    Keywords: Glucosides ; Linum flavum ; 5-methoxypodophyllotoxin ; podophyllotoxin ; Podophyllum hexandrum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The bioconversion of the lignan desoxypodophyllotoxin by cell suspensions of Linum flavum and of Podophyllum hexandrum was investigated. The apolar substrate could be easily dissolved in the culture medium at a concentration of 2 mM by complexation with dimethyl-β-cyclodextrin. Growth parameters of the cell suspensions were not affected by either the addition of cyclodextrin itself, or when cyclodextrin-complexed desoxypodophyllotoxin was present in the medium. The complexed lignan disappeared from the medium within 7 days for both cell cultures. Cellularly only small amounts of desoxypodophyllotoxin were found. After feeding of desoxypodophyllotoxin, the cell culture of L. flavum accumulated 5-methoxypodophyllotoxin and 5-methoxypodophyllotoxin-β-D-glucoside. After 7 days a total maximal content of 2.38% on a dry weight basis of 5-methoxypodophyllotoxin was formed, corresponding with 249 mg l-1 suspension. The highest bioconversion percentage of 52.3% was found at day 14. The desoxypodophyllotoxin-fed culture of P. hexandrum accumulated podophyllotoxin and its β-D-glucoside with a maximal content of 2.87% on a dry weight basis after 9 days, corresponding with 192 mg 1-1 suspension. The highest bioconversion percentage of 33.2% was also found at day 9.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Plant cell, tissue and organ culture 34 (1993), S. 169-175 
    ISSN: 1573-5044
    Keywords: bioconversion ; cyclodextrins ; glucosylation ; lignans ; Linum flavum cell suspensions ; podophyllotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The glucosylation of the cytotoxic lignan podophyllotoxin by cell cultures derived from Linum flavum was investigated. Four cyclodextrins: β-cyclodextrin, γ-cyclodextrin, dimethyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin were used to improve the solubility of podophyllotoxin by complexation. Dimethyl-β-cyclodextrin met our needs the best and the solubility of podophyllotoxin could be enhanced from 0.15 to 1.92 mM, using a podophyllotoxin/cyclodextrin ratio of 1:1. Growth parameters of the cell suspensions were not affected neither by the addition of cyclodextrins alone, nor when complexed podophyllotoxin was dissolved in the medium. The complexed lignan disappeared rapidly from the culture medium, within 24h, under all experimental conditions. Almost simultaneously, between 73 and 100% of detectable podophyllotoxin was bioconverted into podophyllotoxin-β-d-glucoside. A maximal bioconversion rate of 0.51 mmol l-1 suspension day-1 was calculated for the L. flavum cells growing in a medium which included the podophyllotoxin/dimethyl-β-cyclodextrin complex at a final concentration of 1.35 mM.
    Type of Medium: Electronic Resource
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