Acylureas: a new class of barbiturate-like bacterial cytochrome P-450 inducers.
The soluble, cytochrome P-450-dependent fatty acid monooxygenase of Bacillus megaterium ATCC 14581 is induced by phenobarbital and at least twelve other barbiturates (Kim, B.-H. and Fulco, A.J. (1983) Biochem. Biophys. Res. Commun. 116, 843-850). We have since found that the inducer potency of phenobarbital and of six other of these barbiturates was enhanced by adding them to the growth medium prior to sterilization by autoclaving. A similar 'activation' was effected simply by autoclaving these barbiturates in distilled water at pH 8.0. When the hydrolytic products resulting from such treatment of phenobarbital were identified and screened for inducer activity, the major product, 2-phenylbutyrylurea, was found to be 3-5-times more potent than phenobarbital itself. The racemic mixture, (+/-)-2-phenylbutyrylurea was somewhat more active as an inducer than was either of the enantiomers [+/-) or (-] tested singly. Of the other hydrolytic products of phenobarbital, only 2-phenylbutyramide had significant inducer activity (about the same as phenobarbital). Among other ureides tested, two monosubstituted acetylureas (phenylacetylurea and dodecanoylurea) were inactive as inducers, but six of seven disubstituted acetylureas were better inducers than 2-phenylbutyrylurea.
D000880:Anthraquinones; D001410:Bacillus megaterium / Q000201:enzymology*; D001463:Barbiturates / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction / Q000187:drug effects; D006358:Hot Temperature; D006868:Hydrolysis; D006900:Hydroxylation; D010105:Oxygenases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D012996:Solutions; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000880:Anthraquinones; D001463:Barbiturates; D012996:Solutions; C042834:9,10-anthraquinone; C005825:pheneturide; D014508:Urea; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D010634:Phenobarbital