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Synthesis of oleanolic acid dimers linked at C-28 and evaluation of anti-tumor activity.

Abstract：

:Five dimeric oleanolic acids linked at C-28 by 1,6-hexanediamine, or built around the carbon chains of varying lengths between two carboxyl groups were synthesized, to investigate the effect of internal spacer length and species upon the stereochemical features and anti-tumor activity of the resultant bis-oleanolic acids. The IC50 values of these dimeric compounds for cytotoxicity evaluation in vitro against Hep-G2, A549, BGC-823, MCF-7 and PC-3 tumor cell lines, were mainly under 10.0 μM. This result was much better than the inhibition of proliferation against tested tumor cell lines of the monomer oleanolic acid and the commercial anticancer drug 5-fluorouracil. The cytotoxicity selectivity detection revealed that dimer 11c exhibited low cytotoxicity towards normal human liver cell HL-7702. A combination of fluorescence staining observation and flow cytometric analysis indicated that 11c could induce Hep-G2 cell apoptosis. Molecular mechanism studies suggested that 11c induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating effector caspase-3/9 to trigger cell apoptosis. Further studies revealed that 11c caused cell cycle arrest at G1 phase in Hep-G2 cells. Taken together, these results suggest that 11c may be a potential candidate for further cancer research.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Cheng KG,Su CH,Yang LD,Liu J,Chen ZF

doi

10.1016/j.ejmech.2014.10.066

subject

Has Abstract

pub_date

2015-01-07 00:00:00

pages

480-9

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(14)00994-5

journal_volume

89

pub_type

杂志文章

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