Studies On Active Constituents With Selective Inhibition On Tumor Cells Proliferation From The Flowers Of Juglans Regia

Juglans regia Linn is a deciduous arbor plant from the Juglandaceae family.In some folk regions of southern China,the flowers of this plant are used not only as food,but also as a drug to treat malignant tumors.In order to reveal the chemical constituents which have selective inhibitive activities on tumor cell growth,this paper conducted a systematic study on the active constituents of the flower of J.regia.Taking advantages of a variety of chromatographic techniques,78 compounds were isolated from the EtO Ac-soluble fraction of the 95%ethanol extract of the flowers of J.regia.Names and structures of these compounds are listed in Table 1 and Figure 1.The structures were characterized by in-depth spectroscopic examination,mainly including multiple 1D-and 2D-NMR and HRESIMS experiments and analysis.Compounds 1a*-7*,18*-21b*were new or novel compounds.Compound 26 is a new natural product.According to structure patterns,the isolated compounds were classified into naphthalenes(1a*-17),alkaloids(18*-28),diarylheptanoids(29-39),flavonoids(40-51),lignans(52-54),and others(55-70).Compounds 1a*and 1b*,2a*and 2b*,3a*and 3b*,4a*and 4b*,5a*and 5b*,6a*and 6b*,20a*and 20b*,21a*and 21b*are eight pairs of enantiomers as scalemic mixture.These eight scalemic mixtures were resolved and the absolute configurations were assigned via electronic circular dichroism(ECD)data.The structures of compounds la*-2b*are tetralones linked with purines;The structures of compounds 3a*and 3b*are tetralones bonding indole moieties via a carbon-oxygen single bond isolated for the first time;The structures of compounds 4a*-7*are tetralones bonding naphthalene moieties.Besides,alkaloids were also isolated from Juglans for the first time.In the tests for the growth inhibitory activities(GIAs)against five human cancer cell lines and for the effect on normal intestinal epithelial cell-6(IEC-6)cell in vitro,compounds 4*,19*,36,40,42,45,and 46 exhibited significant activity against HCT-116,HepG2,BGC-823,NCI-H1650,and A2780 cell lines.Especially,compounds 4*and 45 are more significant with IC50 values of<10-7mol/L.Also,they exhibited very weak cytotoxicity on the normal IEC-6 cell in vitro,which suggested that these compounds were selective in inhibiting cells growth.