Anti-complement activities of 2,4-bis(2-hydroxybenzamido)benzoic acid and its diacetylated derivatives.

Abstract

Based on the report that 2, 4-bis (2-hydroxybenzamido) benzoic acid (AB-23) inhibits immune hemolysis in vitro, the site of the action of this compound was studied. AB-23 had no effect on the binding of hemolysin to sheep erythrocytes (E). A high concentration of AB-23 was required for inhibition of higher dose C-induced hemolysis. E which escaped hemolysis in the presence of AB-23, were normally hemolyzed by readdition of fresh C after removal of the drug. Inhibition by AB-23 of C fixation to sensitized E was suggested from these results and confirmed by the finding that AB-23 interferes with immune adherence hemagglutination. The effect of AB-23 was apparently not due to chelation of Mg2+ or Ca2+. AB-23, but neither ethylene diamine tetraacetic acid nor ethylene glycol tetraacetic acid showed inhibitory activity even when added 8 or 15 min after C addition. This suggests that AB-23 inhibits the sequence of later components of C from C3 to C9. This possibility was strongly supported by the following finding that AB-23 prevents the consumption of C activity by zymosan via an alternative pathway. Additionally, 2, 4-bis (2-acetoxybenzamido) benzoic acid, which is easily changed to AB-23 in the body, inhibited the passive Arthus reaction in guinea-pigs and also prevented urinary protein excretion in rats after nephrotoxic serum injection in which complement is known to play an important role. These results suggest the anti-complement effect of AB-23 in vivo.