Synthesis and Evaluation of Guanidine-Containing Schiff Base Copper(II), Zinc(II), and Iron(III) Chelates as Trypsin Inhibitors

3-Formyl-4-hydroxyphenylguanidine hydrochloride and its Schiff base copper(II), zinc(II), and iron(III) chelates were synthesized and their inhibitory activity against bovine β-trypsin were determined. Syntheses of Schiff base metal chelates were carried out from 3-formyl-4-hydroxyphenylguanidine, various L-amino acids, and divalent metal acetate. Their structures were established on the basis of spectroscopic evidence and elemental analysis. The inhibitory activity of these chelates against bovine β-trypsin was determined. The guanidine-containing copper(II) and zinc(II) chelates behaved as potent competitive inhibitors of trypsin. However, similar inhibitory activity was not observed for guanidine-containing iron(III) chelates. The inhibition constants (Ki values, ca. 10−5 M) of guanidine-containing Schiff base copper(II) and zinc(II) chelates were slightly lower than those (ca. 10−6 M) of the corresponding amidine-containing Schiff base chelates with regard to bovine trypsin.