Cytotoxic prenylated flavones from the stem and root bark of Daphne giraldii

Qian Sun; Di Wang; Fei-Fei Li; Guo-Dong Yao; Xue Li; Ling-Zhi Li; Xiao-Xiao Huang; Shao-Jiang Song

doi:10.1016/j.bmcl.2016.07.002

Cytotoxic prenylated flavones from the stem and root bark of Daphne giraldii

Bioorg Med Chem Lett. 2016 Aug 15;26(16):3968-72. doi: 10.1016/j.bmcl.2016.07.002. Epub 2016 Jul 1.

Authors

Qian Sun¹, Di Wang¹, Fei-Fei Li², Guo-Dong Yao³, Xue Li⁴, Ling-Zhi Li¹, Xiao-Xiao Huang⁵, Shao-Jiang Song⁶

Affiliations

¹ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
² School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Yangtze River Pharmaceutical (Group) Co., Ltd, Taizhou 225300, People's Republic of China.
³ China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
⁴ School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
⁵ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: xiaoxiao270@163.com.
⁶ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: songsj99@163.com.

PMID: 27400887
DOI: 10.1016/j.bmcl.2016.07.002

Abstract

Three new prenylated flavones (1-3), along with three known analogues (4-6), were isolated from the stem and root bark of Daphne giraldii. Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. The absolute configurations of compounds 2 and 3 were assigned by optical rotation comparison, CD and [Rh2(OCOCF3)4]-induced CD spectral methods. The in vitro cytotoxicity experiments carried out involving five cancer cell lines (U251, A549, HepG2, MCF-7 and Bcap37) showed that 2 markedly inhibited the proliferation of all tested cells with IC50 values ranging from 4.26 to 20.82μM. The preliminary structure-activity relationships of these flavones are discussed. In addition, compound 2 was found to effectively induce apoptosis in HepG2 cells according to a flow cytometry analysis.

Keywords: Apoptosis; Cytotoxicity; Daphne giraldii; Flavone.

MeSH terms

A549 Cells
Antineoplastic Agents, Phytogenic / chemistry*
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / toxicity
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Daphne / chemistry*
Daphne / metabolism
Drug Screening Assays, Antitumor
Flavones / chemistry*
Flavones / isolation & purification
Flavones / toxicity
Hep G2 Cells
Humans
MCF-7 Cells
Magnetic Resonance Spectroscopy
Molecular Conformation
Plant Bark / chemistry
Plant Bark / metabolism
Plant Roots / chemistry
Plant Roots / metabolism
Plant Stems / chemistry
Plant Stems / metabolism
Prohibitins
Structure-Activity Relationship

Substances

Antineoplastic Agents, Phytogenic
Flavones
PHB2 protein, human
Prohibitins