SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis.
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.
Dao
Trong Tuan
TT
BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Le
Thi Van
TV
Nguyen
Phi Hung
PH
Thuong
Phuong Thien
PT
Minh
Pham Thi
PT
Woo
Eun-Rhan
ER
Lee
Kwang Youl
KY
Oh
Won Keun
WK
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*
D045786:Diterpenes, Kaurane; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C447939:SIRT1 protein, human; D056564:Sirtuin 1