EVALUATION OF THE INHIBITORY ACTIVITY ON SERINE AND ASPARTIC PROTEASES OF 4-AMINO-4H-1,2,4-TRIAZOLE AND 5-AMINOTHIAZOLE DERIVATIVES STRUCTURALLY RELATED TO BETA-LACTAM ANTIBIOTICS

Twenty new derivatives of 4-amino-4H-1,2,4-triazole and 5-aminothiazol e have been examined for their inhibitory potential towards serine and aspartic proteases. Upon prolonged incubation with enzyme, the phenyl acetylaminothiazolium salts exhibit progressive, time-dependent inhibi tion of chymotrypsin according to a first-order process. The formation of a tetrahedral transition state-like complex by attack of the activ e-site serine at the C2-position of the pseudobase form of the thiazol ium may be responsible for the observed effect. Triazolium salts appea red to be simple competitive inhibitors of this enzyme, effective in t he mm range concentration. Poor inhibitions of trypsin and pepsin were also obtained in the triazolium series. In spite of their structural analogy with beta-lactams, the selected derivatives failed to inhibit human leucocyte elastase.