Cytotoxic diterpenoids as potential anticancer agents from the twigs of Casearia kurzii

Feng Liu; Qi Zhang; Xueyuan Yang; Yaru Xi; Xuke Zhang; Huimei Wang; Jie Zhang; Muhetaer Tuerhong; Da-Qing Jin; Dongho Lee; Jing Xu; Yasushi Ohizumi; Ling Shuai; Yuanqiang Guo

doi:10.1016/j.bioorg.2019.102995

Cytotoxic diterpenoids as potential anticancer agents from the twigs of Casearia kurzii

Bioorg Chem. 2019 Aug:89:102995. doi: 10.1016/j.bioorg.2019.102995. Epub 2019 May 23.

Authors

Feng Liu¹, Qi Zhang¹, Xueyuan Yang¹, Yaru Xi¹, Xuke Zhang¹, Huimei Wang¹, Jie Zhang², Muhetaer Tuerhong³, Da-Qing Jin⁴, Dongho Lee⁵, Jing Xu⁶, Yasushi Ohizumi⁷, Ling Shuai¹, Yuanqiang Guo⁸

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.
² Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, People's Republic of China.
³ College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, People's Republic of China.
⁴ School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
⁵ Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
⁶ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, People's Republic of China. Electronic address: xujing611@nankai.edu.cn.
⁷ Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai 989-3201, Japan.
⁸ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address: victgyq@nankai.edu.cn.

PMID: 31185389
DOI: 10.1016/j.bioorg.2019.102995

Abstract

A search for bioactive natural products as anticancer lead compounds has led to the isolation of five new clerodane diterpenoids (1-5) from the twigs of Casearia kurzii. Their structures were elucidated by extensive analysis of their NMR, IR, and HRESIMS data, and the absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analysis. The isolates were biologically evaluated and showed cytotoxic activities toward human lung cancer cells (A549), human cervical cancer cells (HeLa), and human hepatocellular carcinoma cells (HepG2). The most active compound (5) with an IC₅₀ value of 5.3 μM against HeLa cells, was found to induce apoptosis and arrest the HeLa cell cycle at G0/G1 stage to exert cytotoxic effects.

Keywords: Apoptosis; Casearia kurzii; Cell cycle; Clerodane diterpenoids; Cytotoxic activities.

Publication types

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

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry*
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology
Apoptosis / drug effects
Casearia / chemistry*
Casearia / metabolism
Cell Line, Tumor
Circular Dichroism
Diterpenes, Clerodane / chemistry*
Diterpenes, Clerodane / isolation & purification
Diterpenes, Clerodane / pharmacology
Drug Screening Assays, Antitumor
G1 Phase Cell Cycle Checkpoints / drug effects
Humans
Magnetic Resonance Spectroscopy
Molecular Conformation
Nuclear Magnetic Resonance, Biomolecular
Plant Stems / chemistry
Plant Stems / metabolism

Substances

Antineoplastic Agents, Phytogenic
Diterpenes, Clerodane