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Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds

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 neolaxif...

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Detalles Bibliográficos
Autores principales: Liu, Jing-Ping, Xiao, Ye-Zhi, Hu, Yu, Li, Xiao-Nian, Wu, Ming-Jiang, Zhao, Yong, Zhao, Yan, Ma, Ze-Jin, Shen, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712212/
https://www.ncbi.nlm.nih.gov/pubmed/31692523
http://dx.doi.org/10.2147/DDDT.S202345
Descripción
Sumario: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.