Metabolism of 9-(2-chlorobenzyl)-, 9-(2-methylbenzyl)- and 9-(2-methoxybenzyl)-adenines by hamster hepatic microsomes.
It was previously found that 9-benzyladenine (BA) was extensively N1-oxidised by animal hepatic microsomes; further, mononitrosubstitution in the phenyl moiety of BA significantly modified the N1-oxidation rates of the corresponding substrates. In order to establish whether the electronic nature or a steric effect of the substituents in the phenyl moiety is the reason for the modification of N1-oxidation rate, the metabolism of some 2'-substituted 9-benzyladenines, i.e. 9-(2-chlorobenzyl)adenine (2CBA), 9-(2-methyl-benzyl)adenine (2MBA) and 9-(2-methoxybenzyl)adenine (2MOBA), by hamster hepatic microsomes was studied. It was found that the N1-oxide was still the major metabolite for 2CBA. However, only minor amounts of N1-oxides were formed during microsomal incubation with 2MBA and 2MOBA. On the other hand, in spite of the higher N1-oxidation rate of 2CBA, its total biotransformation rate was slightly lower than the other two substrates. Like other 9-aralkyladenines previously studied, dealkylation occurred for all three substrates. It was also found that another two metabolites formed in significant amounts in the incubates from both 2MBA and 2MOBA. These metabolites were not fully characterised and their structures unknown.
Liu
D Y
DY
Chelsea Department of Pharmacy, King's College London, University of London, UK.
Liu
Z D
ZD
el-Ghomari
K
K
Gorrod
J W
JW
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet
C111607:9-(2-chlorobenzyl)adenine; C111609:9-(2-methoxybenzyl)adenine; C111608:9-(2-methylbenzyl)adenine; D000225:Adenine