• The Korean Journal of Pharmacology
• /
• v.29 no.1
• /
• pp.131-137
• /
• 1993

Human neutrophil elastase (HNE, EC 3,4,21, 11), a mediator of tissue breakdown, was inhibited by tetracycline, oxytetracycline and demeclocycline. Among them, oxytetracycline showed the most potent inhibitory effect on the activity of HNE. IC50 of this drug at our specific condition was less than 1 mM. Tetracycline inhibited human neutrophil elastase non-competitively, and oxytetracycline inhibited competitively. Ki values of tetracycline and oxytetracycline were 4.9 mM and 0.39 mM, respectively. Structural modified tetracycline, de-dimethylaminotetracycline, which showed no antibiotic activity since the active dimethylamino radical was removed from the position #4 of the tetracycline, showed similar inhibition effect on the activity of human neutrophil elastase to that of tetracycline. Thus, we speculated that inhibition of human neutrophil elastase by tetracyclines was not depended on the dimethylamino radical which is a critical active site for antibiotic effect, rather it was depended on the hydoxyl radical of tetracyclines. Therefore, the property of inhibiting elastase may be an additional molecular biochemical mechanism of action of these drugs at the inflammatory sites.