SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis

TY - JOUR

T1 - SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis

AU - Dao, Trong Tuan

AU - Le, Thi Van

AU - Nguyen, Phi Hung

AU - Thuong, Phuong Thien

AU - Minh, Pham Thi

AU - Woo, Eun-Rhan

AU - Lee, Kwang Youl

AU - Oh, Won Keun

N1 - Georg Thieme Verlag KG Stuttgart.New York.

PY - 2010/7

Y1 - 2010/7

N2 - 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 (212). The structure of the new compound 1 was determined to be ent-11α-acetoxy-7β-hydroxykaur-16-en-15-one based on spectroscopic analyses. Compounds 3, 4, 69, 11, and 12 exhibited SIRT1 inhibitory activity in an in vitro assay, with IC50 values ranging from 16.08±0.11 to 44.34±2.32μ M. This is the first report showing the potential of ent-kaurane diterpenoids as a new class of natural SIRT1 inhibitors.

AB - 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 (212). The structure of the new compound 1 was determined to be ent-11α-acetoxy-7β-hydroxykaur-16-en-15-one based on spectroscopic analyses. Compounds 3, 4, 69, 11, and 12 exhibited SIRT1 inhibitory activity in an in vitro assay, with IC50 values ranging from 16.08±0.11 to 44.34±2.32μ M. This is the first report showing the potential of ent-kaurane diterpenoids as a new class of natural SIRT1 inhibitors.

KW - Croton

KW - Diterpenes, Kaurane

KW - Enzyme Inhibitors

KW - Humans

KW - Molecular Structure

KW - Plant Extracts

KW - Plant Leaves

KW - Sirtuin 1

KW - Letter

KW - Research Support, Non-U.S. Gov't

U2 - 10.1055/s-0029-1240863

DO - 10.1055/s-0029-1240863

M3 - Journal article

C2 - 20178071

SN - 0032-0943

VL - 76

SP - 1011

EP - 1014

JO - Planta Medica

JF - Planta Medica

IS - 10

ER -