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  • Articles: DFG German National Licenses  (4)
  • Metalloproteinase  (2)
  • Physics  (2)
  • 1
    ISSN: 1432-0843
    Keywords: Angiogenesis ; Metalloproteinase ; Tetracycline ; Minocycline ; Doxycycline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC50s of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC50s of 452 μM, 56 μM and 32 μM, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC50 of 290 μM. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and minocycline act by an MMP-independent mechanism. These results have implications for the mechanism of action of tetracycline analogs, particularly where they are being considered for the treatment of disorders of extracellular matrix degradation including periodontal disease, arthritis, and tumor angiogenesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: Key words Angiogenesis ; Metalloproteinase ; Tetracycline ; Minocycline ; Doxycycline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC50s of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC50s of 452 μM, 56 μM and 32 μM, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC50 of 290 μM. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and minocycline act by an MMP-independent mechanism. These results have implications for the mechanism of action of tetracycline analogs, particularly where they are being considered for the treatment of disorders of extracellular matrix degradation including periodontal disease, arthritis, and tumor angiogenesis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Chemistry Edition 23 (1985), S. 2931-2945 
    ISSN: 0360-6376
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Thin films of cured MY720/DDS epoxy resins were treated with blocking reagents for hydroxyl, amine, and epoxide functional groups. Infrared spectroscopy (IR) and differential scanning calorimetry (DSC) were used to monitor the progress of the reaction. Treated films were soaked in distilled water at 30°C for 720 h, and the corresponding moisture absorption determined gravimetrically. Samples treated with N-methyl-N-t-butyldimethylsilyl trifluroacetamide (MTBSTFA) containing 1% t-butyldimethylchlorosilane (TBDMCS) in dimethylsulfoxide (DMSO) at 30°C showed a maximum reduction in the IR peak at 3400 cm-1 (OH and NH) of 39% and a 100% reduction in the epoxide peak at 904 cm, -1. The moisture absorption was 1.9%, a reduction of 58% compared to the untreated films (ca. 4.5%). The reactions show dependencies on time and temperature and are diffusion controlled. Samples treated with trimethylsilyl isocyanate (TMSI) in DMSO a 70°C showed 72% reduction in the 3400 cm-1 IR peak; DSC thermograms do not show an exothermic energy, suggesting that all epoxide groups reacted. These reactions are primarily dependent on time and temperature. The moisture absorption of TMSI treated samples was 1.0% (75% reduction). Samples were also treated with m-trifluoromethyl phenyliscyanate (MTFPI). The reduction in the IR peak at 3400 cm-1 was 9%, but the moisture absorption was 2.4% - a reduction of 47%.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Journal of Polymer Science Part A-1: Polymer Chemistry 7 (1969), S. 2815-2827 
    ISSN: 0449-296X
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aldehydes, when added to mixtures of ethylaluminum dichloride and titanium trichloride under pressure of propylene, have been found to promote either propylation of benzene or stereospecific polymerization of propylene. Selectivity between the two reaction paths is influenced by the molecular structure of the aldehyde. Most aldehydes promote propylation of benzene to cumene and higher isopropyl benzenes. Propylation occurs with or without titanium trichloride present. Substituted aromatic aldehydes with three or more alkyl substituents promote stereospecific polymerization of propylene. Both reactions are dependent upon the ethylaluminum dichloride/aldehyde molar ratio.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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