The lipophilicity, pharmacokinetics, and cellular uptake of different chemically-modified tetracyclines (CMTs).

  title={The lipophilicity, pharmacokinetics, and cellular uptake of different chemically-modified tetracyclines (CMTs).},
  author={Yu Rong Liu and N. S. Ramamurthy and James F. Marecek and H. M. Lee and Jack L.‐Y. Chen and Maria Emanuel Ryan and Barry R. Rifkin and Lorne M. Golub},
  journal={Current medicinal chemistry},
  volume={8 3},
CMTs are analogs of tetracyclines, which are chemically modified to eliminate their antimicrobial efficacy but which retain their inhibitory activity against matrix metalloproteinases. These compounds have been found to inhibit connective tissue breakdown in animal models of diseases such as periodontitis, arthritis and cancer. Because CMTs exhibit different in vivo efficacy in these various models of disease, the current study compared their pharmacokinetics and other properties as follows… Expand
A Chemically Modified Tetracycline (CMT-3) Is a New Antifungal Agent
Several chemically modified tetracycline analogs (CMTs), which were chemically modified to eliminate their antibacterial efficacy, were unexpectedly found to have antifungal properties and CMT-3 appeared to have widespread intracellular distribution throughout C. albicans and the Penicillium sp. Expand
CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export
The results offer promise for therapeutic strategies to combat the effects of hyperpigmentation by use of CMT-308 at low micromolar concentrations and indicate that CMT’s anti-melanogenic action may be attributed to a selective inhibition of melanosome export with the perinuclear aggregation of melanOSomes, rather than a direct effect on the tyrosinase-catalyzed steps in melanin biosynthesis. Expand
Chemically modified tetracyclines as inhibitors of matrix metalloproteinases.
Pre-clinical and early clinical data for one of these CMTs, COL-3 (formerly CMT-3) indicate considerable potential for this group of anticancer agents, and further testing and rational modifications ofThese CMT analogues might lead to new antic cancer agents. Expand
Interaction of chemically modified tetracyclines with catalytic Zn(II) ion in matrix metalloproteinase: evidence for metal coordination sites
Chemically modified tetracyclines (CMTs) have shown promising activity as matrix metalloproteinase (MMP) inhibitors acting as zinc-binding groups. The first step in the design of new and effectiveExpand
Pharmacokinetics of Doxycycline in Ducks with Steatosis due to Force-feeding
The pharmacokinetics of doxycycline was investigated in force-fed and normally fed ducks after single intravenous and oral administration at a dose of 15 mg/kg bw and can be accepted as an information for possible prolonged retention in force fed ducks compared to normally fed ones. Expand
COL-3, a Chemically Modified Tetracycline, Inhibits Lipopolysaccharide-Induced Microglia Activation and Cytokine Expression in the Brain
Administration of chemically modified tetracycline-3 (COL-3), inhibits lipopolysaccharide (LPS)-induced microglial and p38 MAPK activation, as well as the increase in TNF-α, but not IL-1β expression, in the brains of BALB/c mice is found. Expand
Comparative analysis of the effects of a novel vacuolar adenosine 5'-triphosphatase inhibitor, FR202126, and doxycycline on bone loss caused by experimental periodontitis in rats.
  • K. Niikura
  • Chemistry, Medicine
  • Journal of periodontology
  • 2006
It is suggested that an acidic microenvironment plays a more important role than MMPs in periodontal alveolar bone destruction and that V-ATPase inhibitors may offer a new approach to the treatment ofperiodontal disease. Expand
Structural and dynamics analysis of matrix metalloproteinases MMP-2 complexed with chemically modified tetracyclines (CMTs)
Comparison of various relevant molecular aspects of the different complexes of MMP-2 and CMT-n derivatives was performed aiming to elucidate the effect of ligands on the enzyme structure, and helps to understand the differences in the binding modes of related compounds. Expand
Stable anticancer gold(III)-porphyrin complexes: effects of porphyrin structure.
The enhanced stabilization of the gold(III) ion and the ease of structural modification render porphyrins an attractive ligand system in the development of physiologically stable gold( III) complexes with anticancer and anti-angiogenic activities. Expand
A sensitive cell-based assay to measure the doxycycline concentration in biological samples.
This bioassay for the quantification of DOX concentration in biological samples has several advantages over high-performance liquid chromatography-based and microbiological assays: (1) multiple samples can be assayed in a single experiment; (2) only small sample volumes are required; (3) the assay has a low detection limit; and the assay can be performed in any cell culture laboratory. Expand