Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds

Abstract

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

Acknowledgment

This work was supported by grants from the National Natural Science Foundation of China (21462053, 21564018), the Science Foundation of Yunnan Province Office of Education (2014Z044), Program of the Undergraduate Innovation (2018059).

Disclosure

The authors report no conflicts of interest in this work.