title: SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis.
abstract: Silent information regulator two ortholog 1 (SIRT1) is a member of the sirtuin deacetylase family of enzymes that removes acetyl groups from the lysine residues in histones and other proteins. It has been suggested that SIRT1 inhibitors might be beneficial in the treatment of cancer and neurodegenerative diseases. Bioassay-guided fractionation of the MeOH extract of the leaves of CROTON TONKINENSIS resulted in the isolation of a new ENT-kaurane diterpenoid (1) along with 11 known compounds (2- 12). The structure of the new compound 1 was determined to be ENT-11 alpha-acetoxy-7 beta-hydroxykaur-16-en-15-one based on spectroscopic analyses. Compounds 3, 4, 6- 9, 11, and 12 exhibited SIRT1 inhibitory activity in an IN VITRO assay, with IC (50) values ranging from 16.08 +/- 0.11 to 44.34 +/- 2.32 microM. This is the first report showing the potential of ENT-kaurane diterpenoids as a new class of natural SIRT1 inhibitors.
authors.affiliation: BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
authors.forename: Trong Tuan
authors.initials: TT
authors.lastname: Dao
authors.forename: Thi Van
authors.initials: TV
authors.lastname: Le
authors.forename: Phi Hung
authors.initials: PH
authors.lastname: Nguyen
authors.forename: Phuong Thien
authors.initials: PT
authors.lastname: Thuong
authors.forename: Pham Thi
authors.initials: PT
authors.lastname: Minh
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
mesh_terms: D029802:Croton / Q000737:chemistry*; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors*
chemical_list: D045786:Diterpenes, Kaurane; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C447939:SIRT1 protein, human; D056564:Sirtuin 1