Soo-Hyun Cho

Structural requirement of isoflavonones for the inhibitory activity of interleukin-5.

Sophoricoside isolated from Sophora japonica is a glycoside of isoflavonone as an inhibitor of interleukin (IL)-5. To identify structural requirements of this isoflavonone for its inhibitory activity against IL-5, isoflavonones, isoflavanones, and their glycosides were prepared and their inhibitory activity was tested against IL-5. Among them, 5-benzyloxy-3-(4-hydroxyphenyl)chromen-4-one (4b, 87.9% inhibition at 50 microM, IC(50)=15.3 microM) shows the most potent activity, comparable with that of sophoricoside. The important structural requirements of these isoflavonone analogs exhibiting the inhibitory activity against IL-5 were recognized as (1) planarity of chromen-4-one ring, (2) existence of phenolic hydroxyl at 4-position of B ring, and (3) introduction of benzyloxy at 5-position, which may act as a bulky group for occupying hydrophobic pocket in putative binding site. However the glucopyranosyl moiety of sophoricoside is not an essential motif for the activity.

Chemical constituents from Nelumbo nucifera leaves and their anti-obesity effects.

Nelumbo nucifera Gaertn. (Nymphaeaceae), commonly called lotus, is widely distributed throughout Eastern Asia. It has been used for food and medicine for a long time. A phytochemical investigation of N. nucifera leaves led to the isolation of 13 megastigmanes (1-13), including a new megastigmane, nelumnucifoside A (1), and a new eudesmane sesquiterpene, nelumnucifoside B (14), eight alkaloids (15-22), and 11 flavonoids (23-33). Their chemical structures were determined based on spectroscopic methods including 1D, 2D NMR and MS spectrometry. The relative and absolute stereochemistry of the compounds was determined by NOESY and CD spectrometry, respectively. Compounds 19 and 22 significantly inhibited pancreatic lipase, whereas compounds 15 and 16 showed a strong inhibitory effect on adipocyte differentiation. Therefore, the leaves of N. nucifera have potential as an anti-obesity agent by inhibiting pancreatic lipase and adipocyte differentiation.

The role of the hydrophobic group on ring A of chalcones in the inhibition of interleukin-5

Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at 50 μM, IC50=25.3 μM) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds2c (IC50=12.6 μM),2d (IC50=12.2 μM), and2i (IC50=12.3 μM) exhibited the most potent activity. Considering the cLog P values of2, the alkoxy group contributes to the cell permeability of2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of2 should be one that provides the cLog P of2 in the range of 4.22 to 4.67.

Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-catenin pathway

We synthesized (+)-decursin derivatives substituted with cinnamoyl- and phenyl propionyl groups originating from (+)-CGK062 and screened them using a cell-based assay to detect relative luciferase reporter activity. Of this series, compound 8b, in which a 3-acetoxy cinnamoyl group was introduced, most potently inhibited (97.0%) the Wnt/β-catenin pathway. Specifically, compound 8b dose-dependently inhibited Wnt3a-induced expression of the β-catenin response transcription (CRT) and increased β-catenin degradation in HEK293 reporter cells. Furthermore, compound 8b suppressed expression of the downstream β-catenin target genes cyclin D1 and c-myc and suppressed PC3 cell growth in a concentration-dependent manner.

A New Flavolignan from Nelumbo nucifera Leaves

A new flavolignan, isohydnocarpin A (1), together with three known flavolignans, isohydnocarpin (2), hydnocarpin B (3), and hydnocarpin D (4), was isolated from the leaves of Nelumbo nicifera. The structure of the new compound was determined based on spectroscopic methods including 1D and 2D NMR and MS spectrometry. The stereochemistry was determined by NOESY experiments.