10-alpha-aminoacyl-9(10H)-anthracenones: Inhibition of 12(S)-HETE biosynthesis and HaCaT cell growth

1,8-Dihydroxy-9(10H)-anthracenones with a 10-alpha-aminoacyl group were syn thesized using either a mixed-anhydride coupling method or Boc-protected ox azolidinediones. The novel anthracenones were evaluated as inhibitors of th e biosynthesis of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) in epider mal homogenate of mice and for inhibition of the growth of HaCaT keratinocy tes. These cells were also tested for their susceptibility for the action o f the most potent members of this series on plasma membrane integrity, in o rder to confirm that inhibition of cell growth is not a result of membrane damage induced by prooxidants released from anthracenones. Hydroxyl-radical generation as measure of the prooxidant potential of the compounds was det ermined by deoxyribose degradation. The most potent analogues of this serie s were equally potent as anthralin against 12(S)-HETE biosynthesis and kera tinocyte proliferation, while oxygen-radical generation and the resulting d amage to cell membrane was strongly reduced as compared to the antipsoriati c drug.