nitrocatechol and entacapone

nitrocatechol has been researched along with entacapone* in 2 studies

Other Studies

2 other study(ies) available for nitrocatechol and entacapone

ArticleYear
Synergistic inhibition of lung cancer cell lines by (-)-epigallocatechin-3-gallate in combination with clinically used nitrocatechol inhibitors of catechol-O-methyltransferase.
    Carcinogenesis, 2014, Volume: 35, Issue:2

    (-)-Epigallocatechin-3-gallate (EGCG) has exhibited been studied for lung cancer inhibitory activity in vitro and in animal models, but it is rapidly methylated and inactivated by catechol-O-methyltransferase (COMT). Entacapone and tolcapone, COMT inhibitors, are used to mitigate the symptoms of Parkinson's disease. We investigated the synergistic effects of entacapone/tolcapone and EGCG against lung cancer cell lines in culture. EGCG, entacapone and tolcapone inhibited the growth of H1299 human lung cancer cells (IC50 = 174.9, 76.8 and 29.3 µM, respectively) and CL-13 murine lung cancer cells (IC50 = 181.5, 50.7 and 19.7 µM, respectively) as single agents following treatment for 72h. Treatment with 1:10, 1:5, 1:2.5 and 1:1 combinations of EGCG and tolcapone or entacapone resulted in synergistically enhanced growth inhibition. The growth inhibitory effect of the combinations was mediated by induction of intracellular oxidative stress, cell cycle arrest and decreased nuclear translocation of nuclear factor-κΒ. Methylation of EGCG was dose dependently inhibited by entacapone and tolcapone (IC50 = 10 and 20 µM, respectively) in a cell-free system, and both compounds increased the intracellular levels of unmethylated EGCG. Treatment of mice with EGCG in combination with tolcapone increased the bioavailability of EGCG and decreased the methylation of plasma norepinephrine: no apparent liver or behavioral toxicity was observed. In conclusion, the combination of EGCG and entacapone/tolcapone synergistically inhibited the growth of lung cancer cells in culture, and the mechanistic basis for this synergy is likely due in part to inhibition of COMT with resultant increase in the levels of unmetabolized EGCG.

    Topics: Animals; Anticarcinogenic Agents; Apoptosis; Benzophenones; Blotting, Western; Catechin; Catechol O-Methyltransferase Inhibitors; Catechols; Cell Cycle; Cell Proliferation; Cell-Free System; DNA Methylation; Drug Synergism; Enzyme Inhibitors; Humans; Lung Neoplasms; Male; Mice; Nitriles; Nitro Compounds; Nitrophenols; Oxidative Stress; Reactive Oxygen Species; Tolcapone; Tumor Cells, Cultured

2014
Tau-derived-hexapeptide 306VQIVYK311 aggregation inhibitors: nitrocatechol moiety as a pharmacophore in drug design.
    ACS chemical neuroscience, 2013, Dec-18, Volume: 4, Issue:12

    The nitrocatechol derivatives tolcapone (1) and entacapone (2), used as adjunctive therapy in the treatment of Parkinson's disease, were investigated for their potential to inhibit the tau-derived-hexapeptide 306VQIVYK311. They were compared to small molecules that contain similar pharmacophores including the catechol derivatives (dopamine 3 and epinephrine 4), nitroderivatives (nifedipine 5 and chloramphenicol 6), nitrocatechol isomers (7 and 8), and a tolcapone derivative (13) lacking the nitrocatechol moiety. The aggregation kinetics by thioflavin S fluorescence assay indicates that both tolcapone (1) and entacapone (2) exhibit antiaggregation properties. These findings were supported by transmission electron microscopy (TEM) and circular dichroism (CD) spectroscopy measurements which suggest that the nitrocatechol (3,4-dihydroxy-5-nitrophenyl) moiety is a suitable pharmacophore in the design of new tau-aggregation inhibitors. Furthermore, tolcapone (1) was identified as most active compound with antiaggregation activity (46% inhibition of fluorescence intensity at 50 μM), which was supported by TEM data. The in silico steric zipper model of the tau-derived-hexapeptide 306VQIVYK311 indicates that the 3,4-dihydroxy-substituent present in tolcapone (1) and entacapone (2) underwent polar contacts with lysine side chains (VQIVYK), whereas the charged 5-nitrosubstituent was in close contact with lysine side chain present in the steric zipper region suggesting the critical role of a nitrocatechol (3,4-dihydroxy-5-nitrophenyl) pharmacophore present in tolcapone (1) and entacapone (2) in tau-hexapeptide binding and prevention of β-sheet assembly. Our results have significant implications in the design and development of tau-aggregation inhibitors.

    Topics: Antiparkinson Agents; Benzophenones; Catechols; Circular Dichroism; Drug Design; Microscopy, Electron, Transmission; Nitriles; Nitro Compounds; Nitrophenols; Peptide Fragments; tau Proteins; Tolcapone

2013