Τίτλος:
Effect of some biologically interesting substituted tetrahydro-1,4-oxazines on drug metabolising enzymes and on inflammation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The effect on hepatic drug metabolising enzymes was evaluated for three representative structures (1, 2 and 3) that were selected from a series of substituted oxazine derivatives designed to possess particular pharmacological properties such as analgesic, antioxidant and hypolipidemic activity. In addition, since xenobiotic metabolism, reactive oxygen and nitrogen species, atherosclerosis and inflammation are interrelated and mutually affected, the effects of (2) and (3) on acute inflammation in vivo and lipoxygenase activity in vitro were also investigated. It was found that treatment of rats with (1) caused induction of cytochrome P450, enhancement of the metabolism of aminopyrine in vitro and of zoxazolamine and hexobarbital in vivo. Compound (2) appeared to induce particularly erythromycin N-demethylation, while (3), a nitric ester, reduced the catalytically active cytochrome P450, although it increased the metabolism of specific cytochrome P450 substrates, i.e. 4-nitrophenol and erythromycin. Compounds (2) and (3), with strong hypolipidemic and antioxidant properties, reduced acute inflammatory response in two inflammation models and inhibited lipoxygenase activity in vitro. These results are helpful in optimising the biological profile as well as the potential applications of substituted oxazines. © 2005 Bentham Science Publishers Ltd.
Συγγραφείς:
Rekka, E.A.
Kourounakis, A.P.
Avramidis, N.
Kourounakis, P.N.
Περιοδικό:
Current Drug Metabolism
Λέξεις-κλειδιά:
2 (4 biphenyl) 2 (3 nitrooxypropoxy) 4 methylmorpholine; 2 (4 biphenyl) 4 methyloctahydro 1,4 benzoxazin 2 ol; 3 phenyl 3 propoxy octahydro 1,4 pyrido[2,3 c]oxazine; 4 nitrophenol; aminophenazone; cytochrome P450; drug metabolizing enzyme; erythromycin; hexobarbital; lipoxygenase; n demethylase; opiate derivative; oxazine derivative; reactive nitrogen species; reactive oxygen metabolite; tetrahydro 1,4 oxazine derivative; unclassified drug; zoxazolamine, analgesic activity; animal experiment; animal model; animal tissue; antiinflammatory activity; antioxidant activity; atherosclerosis; controlled study; disease association; drug design; drug identification; drug mechanism; drug metabolism; drug structure; drug synthesis; enzyme activity; enzyme induction; enzyme inhibition; in vitro study; in vivo study; inflammation; lipid blood level; nonhuman; paw edema; process optimization; rat; review; substitution reaction; xenobiotic metabolism, Animals; Anti-Inflammatory Agents; Anticholesteremic Agents; Antilipemic Agents; Body Weight; Cytochrome P-450 Enzyme System; Edema; Enzyme Inhibitors; Freund's Adjuvant; Lethal Dose 50; Lipoxygenase Inhibitors; Liver; Mice; Morpholines; Nitric Oxide; Organ Size; Pharmaceutical Preparations; Rats
DOI:
10.2174/138920005774330648
