Pharmacokinetics and Clinical Use of Cephalosporin Antibiotics

Microbial Models of Mammalian Metabolism

Microbial models of mammalian metabolism. Aromatic hydroxylation.

Toluene dioxygenase, a multicomponent enzyme system known to oxidize mononuclear aromatic hydrocarbons to cis-dihydrodiols, oxidized indene and indan to 1-indenol and 1-indanol, respectively. In addition, the enzyme catalyzed dioxygen addition to the nonaromatic double bond of indene to form cis-1,2-indandiol. The oxygen atoms in 1-indenol and cis-1,2-indandiol were shown to be derived from molecular oxygen, whereas 70% of the oxygen in 1-indanol was derived from water. All of the isolated products were optically active as demonstrated by 19F NMR and HPLC discrimination of diastereomeric esters and by chiroptic methods. The high optical purity of (-)-(1R)-indanol (84% enantiomeric excess) and the failure of scavengers of reactive oxygen species to inhibit the monooxygenation reaction supported the contention that the monooxygen insertion is mediated by an active-site process. Experiments with 3-[2H]indene indicated that equilibration between C-1 and C-3 occurred prior to the formation of the carbon-oxygen bond to yield 1-indenol. Naphthalene dioxygenase also oxidized indan to 1-indanol, which suggested that benzylic monoxygenation may be typical of this group of dioxygenases.

Benzylic monooxygenation catalyzed by toluene dioxygenase from Pseudomonas putida

The Influence of Stereochemical Factors on Drug Disposition

Metabolism of acetylmethadol. Sensitive assay for noracetylmethadol and the identification of a new active metabolite

Metabolism of cephalexin-14C in mice and in rats.

In vivo hydroxylation of the alkaloid acronine, an experimental antitumor agent.

Oxidation of indan to indanol and indanone by the hepatic microsomal system

The Dehydrogenation of 1-Indanol by a Soluble Oxidoreductase from Bovine Liver

Ruth E. Billings

Papers

Metabolism of acetylmethadol. Sensitive assay for noracetylmethadol and the identification of a new active metabolite

Metabolism of cephalexin-14C in mice and in rats.

In vivo hydroxylation of the alkaloid acronine, an experimental antitumor agent.

Oxidation of indan to indanol and indanone by the hepatic microsomal system

The Dehydrogenation of 1-Indanol by a Soluble Oxidoreductase from Bovine Liver