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 beta-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 beta-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 (K(i) 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.
Toyota
Eiko
E
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
Sekizaki
Haruo
H
Itoh
Kunihiko
K
Tanizawa
Kazutaka
K
D000596:Amino Acids / Q000737:chemistry; D002412:Cations; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D019216:Metals, Heavy / Q000737:chemistry*; D015394:Molecular Structure; D012545:Schiff Bases / Q000737:chemistry; D014357:Trypsin / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry
C480240:3-formyl-4-hydroxyphenylguanidine hydrochloride; D000596:Amino Acids; D002412:Cations; D002614:Chelating Agents; D005290:Ferric Compounds; D006146:Guanidines; D019216:Metals, Heavy; D012545:Schiff Bases; D014361:Trypsin Inhibitors; D003300:Copper; D014357:Trypsin; D015032:Zinc