Biomaterial Database

Enzymatic ring-opening reactions of the chiral cardioprotective agent (+) (S)-ICRF-187 and its (-) (R)-enantiomer ICRF-186 by dihydropyrimidine amidohydrolase. 1993

B B Hasinoff

Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.

The kinetics of the ring-opening reaction of the cardioprotective agent (+) (S)-ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane, dexrazoxane] and its (-) (R)-analog ICRF-186 by the enzyme dihydropyrimidine amidohydrolase (DHPase) has been studied by HLLC. Chromatographic separation of the two single-ring opened hydrolysis products allowed an estimation of the Michaelis parameters for the opening of each individual ring on the two optical isomers. Under nonsaturating conditions, DHPase acts on ICRF-187 4 times faster than it does on ICRF-186. However, the single-ring opened hydrolysis products of both ICRF-187 and ICRF-186 are not substrates of DHPase. Because the active form of ICRF-187 is thought to be its rings-opened metal ion chelating form, these results suggest that DHPase-catalyzed hydrolysis occurring in the liver and the kidney may lead to differences in the pharmacological action and effectiveness of these two optical isomers.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D011929	Razoxane	An antimitotic agent with immunosuppressive properties.	ICRF-159,ICRF-186,NSC-129943,Razoxane Mesylate, (R)-Isomer,Razoxane, (R)-Isomer,Razoxin,ICRF 159,ICRF 186,ICRF159,ICRF186,NSC 129943,NSC129943
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D006868	Hydrolysis	The process of cleaving a chemical compound by the addition of a molecule of water.
D000581	Amidohydrolases	Any member of the class of enzymes that catalyze the cleavage of amide bonds and result in the addition of water to the resulting molecules.	Amidases,Amidohydrolase
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer