Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii

Jun Ma; Xueyuan Yang; Qi Zhang; Xuke Zhang; Chunfeng Xie; Muhetaer Tuerhong; Jie Zhang; Da-Qing Jin; Dongho Lee; Jing Xu; Yasushi Ohizumi; Yuanqiang Guo

doi:10.1016/j.bioorg.2019.01.048

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii

Bioorg Chem. 2019 Apr:85:558-567. doi: 10.1016/j.bioorg.2019.01.048. Epub 2019 Feb 2.

Authors

Jun Ma¹, Xueyuan Yang¹, Qi Zhang¹, Xuke Zhang¹, Chunfeng Xie¹, Muhetaer Tuerhong², Jie Zhang³, Da-Qing Jin⁴, Dongho Lee⁵, Jing Xu⁶, Yasushi Ohizumi⁷, 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 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.
³ 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.
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. 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: 30807898
DOI: 10.1016/j.bioorg.2019.01.048

Abstract

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A-F (1-6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1-6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2, with an IC₅₀ value of 5.3 μM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the 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*
Cell Line, Tumor
Diterpenes, Clerodane / chemistry
Diterpenes, Clerodane / isolation & purification
Diterpenes, Clerodane / pharmacology*
Drug Screening Assays, Antitumor
G1 Phase Cell Cycle Checkpoints / drug effects
Humans
Plant Leaves / chemistry*
Stereoisomerism

Substances

Antineoplastic Agents, Phytogenic
Diterpenes, Clerodane