title: Effect of structural modification on the inhibitory selectivity of rutaecarpine derivatives on human CYP1A1, CYP1A2, and CYP1B1.
abstract: Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inhibitors. 1-Methoxyrutaecarpine and 1,2-dimethoxyrutaecarpine are the most selective CYP1A2 inhibitors.
authors.affiliation: National Research Institute of Chinese Medicine, 155-1 Li-Nong Street, Sec. 2, Taipei 112, Taiwan, ROC.
authors.forename: Ming-Jaw
authors.initials: MJ
authors.lastname: Don
authors.forename: David F V
authors.initials: DF
authors.lastname: Lewis
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Wang
authors.forename: Mei-Wen
authors.initials: MW
authors.lastname: Tsai
authors.forename: Yune-Fang
authors.initials: YF
authors.lastname: Ueng
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001665:Binding Sites / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065633:Cytochrome P-450 CYP1B1; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D026121:Indole Alkaloids; D008958:Models, Molecular; D008968:Molecular Conformation; D011799:Quinazolines; D013329:Structure-Activity Relationship; D052999:Quinazolinones
chemical_list: D000470:Alkaloids; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065633:Cytochrome P-450 CYP1B1; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones; C585496:CYP1B1 protein, human