Library Construction and Biological Evaluation of Enmein-Type Diterpenoid Analogues as Potential Anticancer Agents

A library of promising enmein-type 14-O-diterpenoid derivatives was constructed from a commercially available kaurene-type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC₅₀ values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel-7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity invivo in studies with a murine model of gastric cancer (MGC-803 mice). These results warrant further preclinical investigations of these diterpenoid-based analogues as potential novel anticancer chemotherapeutics. Dosing with diterpenoids: A synthetic library of enmein-type diterpenoid derivatives with potent antitumor activities was constructed by using commercially available starting materials. The analogue shown here exhibits potent invitro and invivo activities and suitable chemical properties similar to or exceeding those of the parent compound, warranting further preclinical investigations for potential diterpenoid-based anticancer agents.