Enmein-type diterpenoid analogs from natural kaurene-type oridonin: Synthesis and their antitumor biological evaluation

A series of enmein-type diterpenoid analogs (11–20) derived from natural kaurene-type diterpenoid oridonin were synthesized and biologically evaluated. All target compounds showed improved anti-proliferative activities against four human cancer cell lines compared with natural oridonin and parent co...

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Published in:European journal of medicinal chemistry 2013-06, Vol.64, p.215-221
Main Authors: Li, Dahong, Xu, Shengtao, Cai, Hao, Pei, Lingling, Zhang, Hengyuan, Wang, Lei, Yao, Hequan, Wu, Xiaoming, Jiang, Jieyun, Sun, Yijun, Xu, Jinyi
Format: Article
Language:English
Subjects:
Anti-proliferative activity
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Cell Cycle - drug effects
Cell cycle analysis
Cell Line, Tumor
Diterpenes - chemical synthesis
Diterpenes - chemistry
Diterpenes - pharmacology
Diterpenes, Kaurane - chemistry
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enmein-type diterpenoid
Humans
Molecular Conformation
Oridonin
Structure-Activity Relationship
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Summary:A series of enmein-type diterpenoid analogs (11–20) derived from natural kaurene-type diterpenoid oridonin were synthesized and biologically evaluated. All target compounds showed improved anti-proliferative activities against four human cancer cell lines compared with natural oridonin and parent compound 10. Some compounds were more potent than positive control Taxol. Furthermore, mechanistic investigation showed that the representative compound 17 affected cell cycle and induced apoptosis at low micro-molar level in human hepatoma Bel-7402 cells, via an oxidative stress triggered mitochondria-related caspase-dependent pathway. The synthetic enmein-type diterpenoid analog 17 exhibited potent anti-proliferative activities and induced apoptosis via mitochondria-related caspase-dependent pathways. [Display omitted] •Promising enmein-type diterpenoid analogs were obtained from natural oridonin.•All the derivatives showed improved anti-proliferative activities.•The most promising compound 17 was selected for further mechanistic evaluation.•The influence of cell cycle progression by compound 17 was observed.•Inducing of apoptosis involves mitochondria-related caspase-dependent pathways.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2013.04.012