| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1394415 | European Journal of Medicinal Chemistry | 2013 | 7 Pages |
A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a–j) were designed and synthesized. All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-7402 cells with IC50 values of 0.39 μM and 1.39 μM, respectively. The cellular mechanisms showed that compound 12j induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells. These results demonstrate that the spirolactone-type diterpenoid derivatives of oridonin have optimized growth inhibitory activity against cancer cells and interesting apoptosis-inducing ability.
Graphical abstractThe most effective synthetic spirolactone-type diterpenoid analog 12j exhibited similar anti-proliferative activity as the positive control Taxol and induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Spirolactone-type diterpenoids could be got from commercial available oridonin. ► A series of derivatives with improved anti-proliferative activities were synthesized. ► Compound 12j showed similar anti-proliferative activity as Taxol in vitro. ► Induction of apoptosis and influence of cell cycle by 12j were investigated. ► The structure–activity relationships of the derivatives were concluded.
