Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells

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.

The 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 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.