title: Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors.
abstract: A series of trans-stilbene derivatives containing a 3,5-dimethoxyphenyl moiety were prepared through a new efficient solution phase synthetic pathway, and their inhibitory activities were evaluated on human cytochrome P450s (CYP) 1A1, 1A2, and 1B1 to find a potent and selective CYP1B1 inhibitor. We found that a substituent at the 2-position of the stilbene skeleton plays a very important role in discriminating between CYP1As and CYP1B1. Among the compounds tested, the most selective and potent CYP1B1 inhibitor was 2,3',4,5'-tetramethoxystilbene. Compound 7j, 2-[2-(3,5-dimethoxy-phenyl)vinyl]thiophene, showed greater inhibitory activities but had a lower selectivity toward all of the CYP1s tested.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, 28 Yungun, Jongro, Seoul 110-460, Korea. pennkim@snu.ac.kr
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
authors.forename: Hyojin
authors.initials: H
authors.lastname: Ko
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Sungkyu
authors.initials: S
authors.lastname: Jung
authors.forename: Sang Kwang
authors.initials: SK
authors.lastname: Lee
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Chun
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D065633:Cytochrome P-450 CYP1B1; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008566:Membranes; D012044:Regression Analysis; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C444340:1-(2,4-dimethoxyphenyl)-2-(3,5-dimethoxyphenyl)ethene; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D013267:Stilbenes; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1