title: A furanquinone from Paulownia tomentosa stem for a new cathepsin K inhibitor.
abstract: In the search for novel inhibitors of cathepsin K, a new furanquinone compound, methyl 5-hydroxy-dinaphtho[1,2-2'3']furan-7,12-dione-6-carboxylate (1a), showed in vitro inhibitory activities for cathepsin K. Compound 1a was isolated originally from Paulownia tomentosa stem and its derivatives were synthesized. Furanquinone compounds (1a, 1b, 1c and 1d) were also found to be capable of inhibiting cathepsin L, which is closely related to cathepsin K. The inhibitory activity of the parent compound 1a (IC50 = 21 microm) for cathepsin K was slightly higher than those of the other three derivatives that have a methoxy (1b), propoxy (1c) or acetoxy (1d) group (IC50 = 33-66 microm) in the 5-position of compound 1a. This implies that the 5-hydroxyl functional group of 1a may have favorable effects on the reduction potential which are related to the cathepsin K inhibitory activities of furanquinone compounds. Therefore, the cathepsin K inhibitory activity of a new furanquinone compound is proposed.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. youmiep@snu.ac.kr
authors.forename: Youmie
authors.initials: Y
authors.lastname: Park
authors.forename: Jae Yang
authors.initials: JY
authors.lastname: Kong
authors.forename: Heeyeong
authors.initials: H
authors.lastname: Cho
mesh_terms: D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D056668:Cathepsin L / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019684:Magnoliopsida / Q000737:chemistry*; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems; D014197:Trees
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; D009281:Naphthalenes; D010936:Plant Extracts; C402369:methyl-5-hydroxy-dinaphthol(1,2-2',3')-furan-7,12-dione-6-carboxylate; D056668:Cathepsin L; D056657:Cathepsin K