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

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

Department of Biosystems and Biotechnology

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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 IC ₅₀ 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.

Original language	English
Pages (from-to)	558-567
Number of pages	10
Journal	Bioorganic Chemistry
Volume	85
DOIs	https://doi.org/10.1016/j.bioorg.2019.01.048
Publication status	Published - 2019 Apr

Bibliographical note

Funding Information:
This work was supported by the National Key Research and Development Program of China (No. 2018YFA0507204), the National Natural Science Foundation of China (Nos. U1703107, 21642016, and 21372125), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700), Hundred Young Academic Leaders Program of Nankai University, State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No. CMEMR2018-B02), and the Fundamental Research Funds for the Central Universities.

Funding Information:
This work was supported by the National Key Research and Development Program of China (No. 2018YFA0507204 ), the National Natural Science Foundation of China (Nos. U1703107 , 21642016 , and 21372125 ), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700 ), Hundred Young Academic Leaders Program of Nankai University , State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No. CMEMR2018-B02 ), and the Fundamental Research Funds for the Central Universities .

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

Apoptosis
Casearia kurzii
Cell cycle
Clerodane diterpenoids
Cytotoxic activities

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bioorg.2019.01.048

Cite this

@article{32f42894844a4a85b5f7e45d739c17d2,

title = "Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii",

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 IC 50 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",

author = "Jun Ma and Xueyuan Yang and Qi Zhang and Xuke Zhang and Chunfeng Xie and Muhetaer Tuerhong and Jie Zhang and Jin, {Da Qing} and Dongho Lee and Jing Xu and Yasushi Ohizumi and Yuanqiang Guo",

note = "Funding Information: This work was supported by the National Key Research and Development Program of China (No. 2018YFA0507204), the National Natural Science Foundation of China (Nos. U1703107, 21642016, and 21372125), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700), Hundred Young Academic Leaders Program of Nankai University, State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No. CMEMR2018-B02), and the Fundamental Research Funds for the Central Universities. Funding Information: This work was supported by the National Key Research and Development Program of China (No. 2018YFA0507204 ), the National Natural Science Foundation of China (Nos. U1703107 , 21642016 , and 21372125 ), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700 ), Hundred Young Academic Leaders Program of Nankai University , State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No. CMEMR2018-B02 ), and the Fundamental Research Funds for the Central Universities . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = apr,

doi = "10.1016/j.bioorg.2019.01.048",

language = "English",

volume = "85",

pages = "558--567",

journal = "Bioorganic Chemistry",

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AU - Ma, Jun

AU - Yang, Xueyuan

AU - Zhang, Qi

AU - Zhang, Xuke

AU - Xie, Chunfeng

AU - Tuerhong, Muhetaer

AU - Zhang, Jie

AU - Jin, Da Qing

AU - Lee, Dongho

AU - Xu, Jing

AU - Ohizumi, Yasushi

AU - Guo, Yuanqiang

N1 - Funding Information: This work was supported by the National Key Research and Development Program of China (No. 2018YFA0507204), the National Natural Science Foundation of China (Nos. U1703107, 21642016, and 21372125), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700), Hundred Young Academic Leaders Program of Nankai University, State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No. CMEMR2018-B02), and the Fundamental Research Funds for the Central Universities. Funding Information: This work was supported by the National Key Research and Development Program of China (No. 2018YFA0507204 ), the National Natural Science Foundation of China (Nos. U1703107 , 21642016 , and 21372125 ), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700 ), Hundred Young Academic Leaders Program of Nankai University , State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No. CMEMR2018-B02 ), and the Fundamental Research Funds for the Central Universities . Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/4

Y1 - 2019/4

N2 - 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 IC 50 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.

AB - 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 IC 50 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.

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KW - Cell cycle

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KW - Cytotoxic activities

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M3 - Article

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SN - 0045-2068

VL - 85

SP - 558

EP - 567

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

ER -

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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