Biochemical properties of anti-inflammatory drugs—VII. Inhibition of proteolytic enzymes in connective tissue by chloroquine (resochin) and related antimalarial/antirheumatic drugs

A chondromucoprotease present in bovine cartilage, with optimal activity at pH 5, has been partially characterized. This autolytic enzyme was irreversibly inhibited by chloroquine, those of its metabolites with a quinoline nucleus, and mepacrine (quinacrine, atebrine). These drugs did not affect cartilage degradation by a mucopolysaccharase (ovine hyaluronidase) or papain. At relatively high concentrations (10 mM), chloroquine and some of its metabolites inhibited rat skin collagenase, a presumed collagenase in bovine cartilage and a bacterial collagenase (clostridiopeptidase A). This drug action was reversible and non-competitive with the substrate, when this was gelatine. Rivanol and acetyl ammonium salts (0·25 mM) were powerful inhibitors of clostridiopeptidase A. Other types of anti-inflammatory (antirheumatic) drugs did not inhibit either the chondromucoprotease or the collagenases. A neutral sulphydryl-dependent esterase in bovine nasal cartilage was inhibited high levels of chloroquine. Chloroquine and hydroxychloroquine were metabolised (de-ethylated) by bovine cartilage incubated at pH 7·4. The possible value of (a) chloroquine and mepacrine for treating degenerative arthritis, and of (b) cetyl ammonium salts for treating clostridial infections, is discussed.