1. Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii
- Author
-
Jie Zhang, Chunfeng Xie, Xueyuan Yang, Qi Zhang, Dongho Lee, Jing Xu, Jun Ma, Yasushi Ohizumi, Yuanqiang Guo, Xuke Zhang, Muhetaer Tuerhong, and Da Qing Jin
- Subjects
Casearia ,Apoptosis ,01 natural sciences ,Biochemistry ,Diterpenes, Clerodane ,HeLa ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Cytotoxic T cell ,Molecular Biology ,A549 cell ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Cancer ,Stereoisomerism ,Cell cycle ,biology.organism_classification ,medicine.disease ,Antineoplastic Agents, Phytogenic ,G1 Phase Cell Cycle Checkpoints ,0104 chemical sciences ,Plant Leaves ,010404 medicinal & biomolecular chemistry ,Cell culture ,Drug Screening Assays, Antitumor - 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.
- Published
- 2019