Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids

Eur J Med Chem. 2017 Jun 16:133:319-328. doi: 10.1016/j.ejmech.2017.03.053.

Chengyuan Liang ¹, Shaomeng Pei ², Weihui Ju ², Minyi Jia ², Danni Tian ², Yonghong Tang ³, Gennian Mao ⁴

Affiliations

1 Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China; Xi'an Taikomed Pharmaceutical Technology Co., LTD, Xi'an 710077, People's Republic of China. Electronic address: chengyuanliang@gmail.com.
2 Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.
3 Xi'an Taikomed Pharmaceutical Technology Co., LTD, Xi'an 710077, People's Republic of China.
4 Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China. Electronic address: maogn@sust.edu.cn.

PMID: 28395218 DOI: 10.1016/j.ejmech.2017.03.053

Abstract

Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC₅₀ = 4.23 ± 0.79 μM) in the G2/M phase and induced cellular Apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated Apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 Family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, Caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.

Keywords

Akt/Bcl-2; Antitumour; Apoptosis; Bergenin; Cinnamic acid.

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