Comparison of metabolic rates of some 9-aralkyladenines obtained using hamster hepatic microsomes

Previous investigations have revealed that N1-oxidation is a major metabolic pathway in vitro for some 9-aralkyladenines (AAs) such as 9-benzyladenine (BA). However, dealkylation and other metabolic pathways are also involved. In addition, various substituents on the benzyl moiety of BA seem to have a marked effect on the metabolic rate. In order to establish the potential structure-metabolism relationship of this class of compounds, the enzyme kinetics of the substrates, which possess 2'-nitro (2NBA), 3'-nitro (3NBA), 4'nitro (4NBA), 2'-chloro (2CBA), 2'-methyl (2MBA), or 2-methoxy (2MOBA) substitution of the benzyl moiety of BA, were compared using hamster hepatic microsomes. The results show that the formation rates of the N1-oxides are in the order 2NBA > 2CBA > BA > 3NBA and 4NBA > 2MBA and 2MOBA; the formation rates of the total metabolites except N1-oxides are in the order 2MOBA and 2MBA > 2CBA > BA > 4NBA > 3NBA > 2NBA; however, the total biotransformation rates of the substrates are in the order 2MBA and 2MOBA > 2CBA > BA and 2NBA > 4NBA > 3NBA. The results strongly imply that the electronic, steric and other physicochemical properties are potential controlling factors for AA metabolism.