Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: biochemical assessment in vitro and ex vivo.
作者： J.E. Tateson , R.W. Randall , C.H. Reynolds , W.P. Jackson , P. Bhattacherjee
DOI: 10.1111/J.1476-5381.1988.TB11557.X
关键词:
摘要: 1. The chemically novel acetohydroxamic acids, BW A4C, A137C and A797C, are potent inhibitors of the synthesis leukotriene B4 (LTB4) from arachidonic acid by human leucocyte homogenates: concentrations required for 50% inhibition (IC50) were 0.1 microM, 0.8 microM 0.5 respectively. Inhibition was less at higher acid. 2. These compounds also inhibited [14C]-5-HETE [14C]-arachidonic calcium-dependent LTB4 5-HPETE. This, therefore, suggests that they inhibit 5-lipoxygenase LTA4 synthase. 3. Concentrations acids to metabolism cyclo-oxygenase, 12-lipoxygenase 15-lipoxygenase 10 100 times than those 5-lipoxygenase. 4. induced ionophore, A23187, in intact leucocytes. This reversed washing cells. They potent, selective A23187 whole rat blood: binding plasma proteins did not greatly reduce effectiveness compounds. 5. effects administered either intravenously or orally rats, on LTB4, thromboxane B2 (TXB2) A23187-stimulated blood ex vivo studied. three caused dose-dependent but TXB2. persisted up 6 h after a single oral dose 50 mg kg-1. 6. unchanged compound determined h.p.l.c. correlated with vivo.
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