Background: Neolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure–activity relationship studies, the α,β-unsaturated ketone (enone) system is an important active group.
Methods: Seven neolaxiflorin B derivatives containing α,β-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay.
Results: Compound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells.
Conclusion: This study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.
Keywords: neolaxiflorin B inspired compounds, unsaturated ketone, antitumor activity