Inhibition of redox cycling of methoxatin (PQQ), and of superoxide release by phagocytic white cells.

The iodonium compounds diphenyleneiodonium and diphenyliodonium, and the amine compounds, 4,5-dimethyl phenylene diamine, N,N-dimethyl 1,4-phenylene diamine, 1,2-diamino-4,5-methyleneoxybenzene, and aminomalononitrile inhibit methoxatin's (PQQ's) redox activity in vitro, that is, the methoxatin-coupled oxidation of glycine and reduction of nitroblue tetrazolium to formazan. The compounds mentioned above also inhibit phorbol myristate acetate (PMA) stimulated superoxide release by phagocytic white cells--determined mainly as the superoxide dismutase sensitive reduction of ferricytochrome C. Related compounds, 3,4-diaminopyridine and 4-dimethylamino-benzylamine, did not inhibit redox activity of PQQ in vitro, nor did they inhibit PMA stimulated superoxide production in monocytes or neutrophils. Thus, there is a correlation between an agent's ability to inhibit PQQ redox cycling and its ability to inhibit superoxide release by phagocytes. The findings are a further indication that PQQ is involved in the respiratory burst of phagocytic cells.