Cytisine-Pterocarpan Derived Compounds: Biomimetic Synthesis and Apoptosis-Inducing Activity in Human Breast Cancer Cells

Abstract

Cytisine-pterocarpan derived compounds were biomimetically synthesized with (-)-cytisine and (-)-maackiain via a N,N-4-dimethyl-4-aminopyridine (DMAP)-mediated synthetic strategy in a mild manner. In the present study, tonkinensine B (4) was elaborated in good and high yields with the optimized reaction conditions. The in vitro cytotoxicity of compound 4 was evaluated against breast cancer cell lines and showed that 4 had a better cytotoxicity against MDA-MB-231 cells (IC50 = 19.2 μM). Depending on the research on cytotoxicities of 4 against RAW 264.7 and BV2 cells, it was suggested that 4 produced low cytotoxic effects on the central nervous system. Further study indicated that 4 demonstrated cytotoxic activity against MDA-MB-231 cells and the cytotoxic activity was induced by apoptosis. The results implied that the apoptosis might be induced by mitochondrion-mediated apoptosis via regulating the ratio of Bax/Bcl-2 and promoting the release of cytochrome c from the mitochondrion to the cytoplasm in MDA-MB-231 cells.

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

“…The majority of approved anticancer drugs are unmodified natural products or semi-synthetic derivatives, and natural products are considered a promising source for future drugs [10,11]. Cytisine is a natural quinolizidine alkaloid that is abundant in the roots of Papilionaceae and Caesalpinioideae, medicinal plants that have been used in traditional Chinese medicine [12].…”

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL‐induced osteoclastogenesis

“…[24][25][26][27] Cytisine is an alkaloid that was found in plants and seeds of the Leguminosae (Fabaceae) family and has been shown to have several multipotent pharmacological activities. [13][14][15][16][17][18][19][20] However, there are NFATc1 is an important transcription factors in osteoclast differentiation. 10 NFATc1 is an NFAT family member that has been reported to modulate expression of several osteoclast-related genes including TRAP, cathepsin K and MMP-9.…”

“…18 In addition, Cytisine has been implied to exert anti-tumour effects on lung cancer cells by regulating reactive oxygen species-induced and MAPK, NF-κB signalling pathways 19 and inhibited human breast cancer cells through apoptosis-induced activity. 20 However, both the function of treatment for osteoporosis and the mechanism by Cytisine suppresses OCs have not yet been studied. So, we managed this study to detect whether Cytisine has the protecting function of ovariectomy-induced bone loss and the possible deeper molecular mechanism.…”

Identification of a cytisine-based EED-EZH2 protein-protein interaction inhibitor preventing metastasis in triple-negative breast cancer cells

“…Cytisine derivatives have shown promising biological activity for the treatment of various diseases, such as nicotine and alcohol dependency, cancers, and neurodegenerative diseases [34]. A cytisine-based inhibitor has been found to exhibit potent anti-proliferation effects against breast cancer cells through suppressing H3K4me3 and p27 expression [35,36]. However, no biological activity of compound 1 itself had been reported.…”