Lee, H Yeom, H Kim, YG Yoon, CN Jin, CB Choi, JS Kim, BR Kim, DH 2024-01-21T17:06:46Z 2024-01-21T17:06:46Z 2021-09-03 1998-05-01 0006-2952 https://pubs.kist.re.kr/handle/201004/143076 The effects of flavonoids on caffeine N3-demethylation, a marker activity of CYP1A2, in human liver microsomes were investigated to elucidate the inhibition mechanism and the structure-activity relationship. Caffeine N3-demethylase activity was inhibited by the presence of various flavonoids, whose structures seem to be closely related to the degree of inhibition. Among twenty-one compounds tested, the most active was ckrysin with an IC50 value of 0.2 mu M. Others had IC50 values ranging from 1 to more than 500 mu M. Kinetic analysis revealed that the mechanism of inhibition varied among the flavonoids. The inhibitory effect was postulated to be governed by factors such as the number of hydroxyl groups and glycosylation of these free hydroxyl groups. An increase in the number of free hydroxyl groups reduced the inhibitory effect on P450 activity. Analysis of the quantitative structure-activity relationship (QSAR) showed that the volume to surface area ratio was the most effective factor on the inhibition of caffeine N3-demethylation, and the electron densities on the C3 and C4' atoms exercised significant influence on the inhibitory effect. The calculated inhibitory effect of flavonoids on CYP1A2 activity was highly correlated with the antimutagenicity of flavonoids on 2 amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ)-induced umu response. (C) 1998 Elsevier Science Inc. English PERGAMON-ELSEVIER SCIENCE LTD HETEROCYCLIC AMINE MUTAGENS HUMAN-LIVER-MICROSOMES PLANT FLAVONOIDS METABOLISM CYTOCHROME-P-450 BENZO(A)PYRENE ACTIVATION ASSAY RATS FOOD Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids Article 10.1016/S0006-2952(97)00644-8 1 BIOCHEMICAL PHARMACOLOGY, v.55, no.9, pp.1369 - 1375 BIOCHEMICAL PHARMACOLOGY 55 9 1369 1375 scie scopus 000073394500005 2-s2.0-0032499398 Pharmacology & Pharmacy Pharmacology & Pharmacy Article HETEROCYCLIC AMINE MUTAGENS HUMAN-LIVER-MICROSOMES PLANT FLAVONOIDS METABOLISM CYTOCHROME-P-450 BENZO(A)PYRENE ACTIVATION ASSAY RATS FOOD flavonoids caffeine N3-demethylation inhibition QSAR