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 |
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Pages (from-to) | 558-567 |
Number of pages | 10 |
Journal | Bioorganic Chemistry |
Volume | 85 |
DOIs | |
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