Biomaterial Database

Serum-catalyzed hydrolysis of metronidazole amino acid esters. 1985

M J Cho, and L C Haynes

Glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), phenylalanine (Phe), and lysine (Lys) esters of metronidazole were synthesized using dicyclohexylcarbodiimide (DCC) coupling or a mixed-anhydride route, using tert-butyloxycarbonyl (tert-Boc) amino acids. Human serum-catalyzed hydrolysis of these esters at 37 degrees C give half-lives varying from 4.5 min for the Phe ester to 96 h for the Ile ester. Also determined was the pH-rate profile for hydrolysis in aqueous buffers at 25 degrees C. A linear relationship was observed between the logarithmic value of the hydrolysis rate constant in serum and that of the OH- -catalyzed hydrolysis of cationic esters. This finding may indicate that the esters studied are "equally" poor substrates for binding to the enzymes in serum and, thus, the difference observed in the serum-catalyzed hydrolysis rate is solely derived from the chemical lability of an ester bond. Interestingly, the extent of chemical activation observed in the buffer system appears to be amplified in the serum-catalyzed hydrolysis.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008795	Metronidazole	A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS.	2-Methyl-5-nitroimidazole-1-ethanol,Bayer 5360,Clont,Danizol,Flagyl,Gineflavir,Metric,MetroGel,Metrodzhil,Metrogyl,Metronidazole Hydrochloride,Metronidazole Monohydrochloride,Metronidazole Phosphate,Metronidazole Phosphoester,Satric,Trichazol,Trichopol,Trivazol,Vagilen,2 Methyl 5 nitroimidazole 1 ethanol
D002021	Buffers	A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer.	Buffer
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D004952	Esters	Compounds derived from organic or inorganic acids in which at least one hydroxyl group is replaced by an –O-alkyl or another organic group. They can be represented by the structure formula RCOOR’ and are usually formed by the reaction between an acid and an alcohol with elimination of water.	Ester
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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.
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino