Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities

Yue Liang; Qi Zhang; Xueyuan Yang; Ying Li; Xuke Zhang; Yuhao Li; Qing Du; Da-Qing Jin; Jianlin Cui; Namrita Lall; Muhetaer Tuerhong; Dongho Lee; Munira Abudukeremu; Jing Xu; Ling Shuai; Yuanqiang Guo

doi:10.1016/j.bioorg.2020.103741

Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities

Bioorg Chem. 2020 May:98:103741. doi: 10.1016/j.bioorg.2020.103741. Epub 2020 Mar 9.

Authors

Yue Liang¹, Qi Zhang¹, Xueyuan Yang¹, Ying Li¹, Xuke Zhang¹, Yuhao Li², Qing Du³, Da-Qing Jin², Jianlin Cui², Namrita Lall⁴, Muhetaer Tuerhong⁵, Dongho Lee⁶, Munira Abudukeremu⁵, Jing Xu⁷, 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 School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
³ Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai Nationalities University, Xining 810007, People's Republic of China.
⁴ Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa.
⁵ 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.
⁶ Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
⁷ 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, Guilin 541004, People's Republic of China. Electronic address: xujing611@nankai.edu.cn.
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: 32213364
DOI: 10.1016/j.bioorg.2020.103741

Abstract

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new and two known clerodane diterpenoids from the leaves of Casearia kurzii. Their structures were elucidated using NMR techniques and electronic circular dichroism (ECD) calculations. The subsequent biological cytotoxicity evaluation of these isolates toward human lung cancer A549, human cervical cancer HeLa, human chronic myeloid leukemia K562, and human hepatocellular carcinoma HepG2 was carried out. The most active compound 4 with an IC₅₀ value of 9.7 μM against HepG2 cells was selected to examine the cytotoxic mechanism, which induced the apoptosis and arrested the HepG2 cell cycle at S stage. The in vivo zebrafish experiments revealed that compound 4 had the property of inhibiting tumor proliferation and migration.

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

Publication types

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

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Casearia / chemistry*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Disease Models, Animal
Diterpenes / chemistry
Diterpenes / isolation & purification
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Neoplasms, Experimental / drug therapy
Neoplasms, Experimental / pathology
Plant Leaves / chemistry
Structure-Activity Relationship
Zebrafish

Substances

Antineoplastic Agents, Phytogenic
Diterpenes