EFFECTS OF AROMATIC AND NONAROMATIC MODEL COMPOUNDS AND DRUGS ON ENZYMIC ACTIVITIES

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois

Purified alcohol-, glutamic- and glucose-6-phosphate dehydrogenases, catalase and carboxypeptidase B were inhibited by simple aromatic compounds; aromatic multi-ring compounds (naphthalene, 2-naphthol, 2-naphthalenesulfonic acid) inhibited invariably at lower concentrations than compounds containing one aromatic ring (benzene, phenol, benzenesulfonic acid). Saturated one-ring compounds (dioxane, cyclohexanol, cyclohexanone) did not impair enzymic activities. In all cases, inhibition was not related to functional groups but could be correlated with aromatic and/or planar properties of the inhibitor molecules. Purified carbonic anhydrase, peroxidase and carboxypeptidase A were not inhibited by any of the above compounds indicating that sensitivity to aromatic moieties was not a common property of all of the enzymes tested.

The same pattern of enzyme inhibition was obtained with a variety of aromatic and nonaromatic drugs, B vitamins and analogs (propylhexadrine, menthol, inositol, biotin, desthiobiotin and procaine, acetylsalicylic acid, sulfanilamide, pyridoxine, pyridoxamine, pyridoxal, desoxypyridoxine and dibucaine, chloroquine, quinacrine, chlorpromazine, 9-aminoacridine, folic acid, aminopterin, riboflavin). While carboxypeptidase A and peroxidase were not inhibited by any of these compounds, the enzymic activities of carboxypeptidase B and of catalase were abolished by compounds containing aromatic moieties.

Inhibition of the activities of canboxypeptidase B and catalase by aromatic compounds was instantaneous and reversible. Kinetic data were complex but essentially identical for all compounds. Since aromatic moieties were the sole common feature of the inhibitor molecules, aromatic properties may well have been responsible for inhibition.