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Jinsart W, Ternai B, Polya GM: Inhibition of myosin light chain kinase, cAMP-dependent protein kinase, protein kinase C and of plant Ca (2+)-dependent protein kinase by anthraquinones. Biol Chem Hoppe Seyler. 1992 Sep;373(9):903-10.
A variety of anthraquinone (anthracene-9,10-dione) derivatives inhibits rat brain Ca (2+)- and phospholipid-activated protein kinase C (PKC) of which the most potent inhibitors are mitoxantrone (1,4-dihydroxy-5,8-bis [2-(hydroxyethylamino)-ethylamino]-9,10- anthracenedione) (IC50 4 microM) and quinalizarin (1,2,5,8-tetrahydroxy-anthraquinone (IC50 4 microM). Anthraquinone derivatives with less polar substitution in positions 1 to 4 and 5 to 8 are less effective as inhibitors of PKC. Wheat germ Ca (2+)-dependent protein kinase (CDPK) assayed with a myosin light chain-based peptide substrate is much less sensitive to inhibition by anthraquinones, the most effective anthraquinone inhibitors being the 1,2,4-trihydroxy (IC50 14 microM), 1,8-dihydroxy-3-methyl (IC50 56 microM) and 1,2,5,8-tetrahydroxy (IC50 65 microM) derivatives. Ca (2+)-calmodulin-dependent myosin light chain kinase (MLCK) is inhibited by a range of di-, tri- and tetrahydroxylated anthraquinones (IC50 values 2 to 53 microM), the most potent inhibitors being the more polar compounds, namely mitoxantrone (IC50 2 microM) and emodin (1,3,8-trihydroxy-6-methylanthraquinone) (IC50 8 microM). Mitoxantrone interacts with calmodulin as determined from abolition of Ca (2+)-dependent fluorescence enhancement of dansyl-calmodulin (IC50 4 microM). A range of anthraquinone derivatives inhibits the catalytic subunit of cAMP-dependent protein kinase (cAK). In a number of cases compounds acting as potent inhibitors of MLCK (such as mitoxantrone and emodin) are very poor inhibitors of cAK and vice versa. |
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