In vitro metabolic N- and C-oxidation of phenanthridine. 1997

N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Marmara, Haydarpasa, Istanbul, Turkey.

The in vitro microsomal metabolism of phenanthridine has been studied to establish as to whether phenanthridine produces the corresponding N-oxide and lactam as metabolites and the mechanism involved. We now report our preliminary findings using rat hepatic microsomal preparations (control and induced with phenobarbitone) fortified with NADPH. The potential metabolite, phenanthridine-N-oxide, was prepared by m-CPBA oxidation of substrate; the lactam was commercially available. The substrate and metabolites were extracted and analysed by HPLC and TLC. Five metabolites, i.e. the corresponding N-oxide, lactam and three other products, were detected. Both N-oxide and lactam metabolites showed identical chromatographic behaviour and UV spectrum--using a multi-array UV detector linked to a HPLC system--as the authentic compounds. The uncharacterised metabolites are proposed to be phenolic because of their chromatographic behaviour and response to detection reagents. The amount of N-oxide and lactam formed was significantly increased when phenobarbitone induced rat microsomes were used as enzyme source. The results indicate that these latter metabolites are probably formed by a phenobarbitone inducible CYP450 isozyme. It may be that the lactam was produced via the N-oxide and experiments are under way to investigate the proposed pathway.

UI MeSH Term Description Entries
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D010617 Phenanthridines
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
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
D002855 Chromatography, Thin Layer Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Thin-Layer,Thin Layer Chromatography,Chromatographies, Thin Layer,Chromatographies, Thin-Layer,Thin Layer Chromatographies,Thin-Layer Chromatographies,Thin-Layer Chromatography
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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.
D013056 Spectrophotometry, Ultraviolet Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Ultraviolet Spectrophotometry

Related Publications

N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
January 1989, Drug metabolism and drug interactions,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
January 1979, Xenobiotica; the fate of foreign compounds in biological systems,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
August 1982, Xenobiotica; the fate of foreign compounds in biological systems,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
October 1987, The Journal of pharmacy and pharmacology,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
February 1987, Xenobiotica; the fate of foreign compounds in biological systems,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
November 1980, Journal of medicinal chemistry,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
February 2002, Phytotherapy research : PTR,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
December 1974, The Journal of pharmacy and pharmacology,
N Tunç, and F Yilmaz, and M Ulgen, and J W Gorrod
January 1989, Drug metabolism and drug interactions,
Copied contents to your clipboard!