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 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.

• Authors: 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
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 85 Pg. 558-567 (04 2019) ISSN: 1090-2120 [Electronic] United States
• PMID: 30807898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Diterpenes, Clerodane

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Casearia (chemistry)
• Cell Line, Tumor
• Diterpenes, Clerodane (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Plant Leaves (chemistry)
• Stereoisomerism