Seong Su Hong

Monoamine oxidase inhibitory components fromCayratia japonica

Seven flavonoids were isolated from the whole plants and fruits ofCayratia japonica through the activity-guided isolation of a methanol extract using a monoamine oxidase (MAO) inhibition assay as a monitor. The chemical structures of the isolates were assigned as apigenin-7-O-β-D-glucuronopyranoside (1), apigenin (2), luteolin (3), luteolin-7-O-β-D-glucopyranoside (4), (+)-dihydroquercetin (taxifolin) (5), (+)-dihydrokaempferol (aromadendrin) (6) and quercetin (7). Among the isolated compounds, flavones such as apigenin (2) and luteolin (3), as well as the flavonol, quercetin (7) showed potent inhibitory effects against the MAO activity with IC50 values of 6.5, 22.6, and 31.6 μM, respectively. However, the flavone glycosides, apigenin-7-O-β-D-glucuronopyranoside (1) and luteolin-7-O-β-D-glucopyranoside (4), showed mild MAO inhibition (IC50 values: 81.7 and 118.6 μM, respectively). The flavanonol derivatives, taxifolin (5) and aromadendrin (6), also showed weak inhibition (IC50 values: 154.7 and 153.1 μM, respectively). Furthermore, quercetin (7) had a more potent inhibitory effect on MAO-A (IC60 value: 2.8 μM) than MAO-B (IC50 value: 90.0 μ.M). Apigenin (2) and luteolin (3) also preferentially inhibited MAO-A (IC50 values: 1.7 and 4.9 μM, respectively) compared with MAO-B (IC50 values: 12.8 and 59.7 μM, respectively).

Monoamine oxidase inhibitory components from the roots of Sophora flavescens

In our search for monoamine oxidase (MAO) inhibitors from natural resources, we found that the methanol extract of the roots ofSophora flavescens showed an inhibitory effect on mouse brain monoamine oxidase (MAO). Bioactivity-guided isolation of the extract yielded two known flavonoids, formononetin (1) and kushenol F (2), as active compounds along with three inactive compounds, oxymatrine (3), trifolirhizin (4), and β-sitosterol (5). Formononetin (1) and kushenol F (2) showed significant inhibitory effects on MAO in a dose-dependent manner with IC50 values of 13.2 and 69.9 μM, respectively. Formononetin (1) showed a slightly more potent inhibitory effect against MAO-B (IC50: 11.0 μM) than MAO-A (IC50: 21.2 μM). Kushenol F (2) also preferentially inhibited the MAO-B activity than MAO-A activity with the IC50 values of 63.1 and 103.7 μM, respectively.

Monoamine oxidase inhibitory constituents from the fruits of Cudrania tricuspidata.

A methylene chloride soluble fraction of the fruits ofCudrania tricuspidata significantly inhibited the mouse brain monoamine oxidase (MAO). Three known prenylated isoflavones were isolated and identified by activity-guided fractionation. Gancaonin A (1), 4′-O-methylalpinumi-soflavone (2), and alpinumisoflavone (3) inhibited MAO activity in a concentration-dependent manner with IC50 values of 19.4, 23.9, and 25.8 μM, respectively. Of these, gancaonin A (1) showed a selective and potent inhibitory effect against -B (IC50 0.8 μ?) than -A (IC50 >800 μM). The kinetic analysis using Lineweaver-Burk plots indicated that gancaonin A (1) competitively inhibited MAO-B.

ent-Kaurane Diterpenoids from Isodon japonicus

Five ent-kaurane diterpenoids, 6beta,7beta,14beta-trihydroxy-1alpha,19-diacetoxy-7alpha,20-epoxy- ent-kaur-16-en-15-one (1), 1alpha,6beta,7beta-trihydroxy-11alpha,19-diacetoxy-7alpha,20-epoxy-ent-kaur-16-en-15-one (2), 6-hydroxy-1alpha,19-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide (3), 19-hydroxy-1alpha,6-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (4), and 6-aldehyde-1alpha,19-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (5), along with 10 known ent-kaurane diterpenoids, pseurata C (6), longikaurin C (7), effusanin C (8), longikaurin B (9), longikaurin D (10), effusanin D (11), excisanin B (12), lasiokaurin (13), megathyrin A (14), and loxothyrin A (15), were isolated from the aerial parts of Isodon japonicus. Their structures were determined on the basis of spectroscopic (1D-, 2D-NMR and MS) and chemical evidence. The isolates were evaluated for their inhibitory effects on LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells.

Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues

Tailor made: We report the rational biosynthesis of C15 hydroxylated non‐quinone geldanamycin analogues by site‐directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post‐PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound.

Monoamine oxidase inhibitory coumarins from the aerial parts of Dictamnus albus.

The methanol extract from the aerial parts ofDictamnus albus was active in inhibiting monoamine oxidase (MAO) from the mouse brain. Activity-guided fractionation led to the isolation of four known coumarins, 7-(6′R-hydroxy-3′, 7′-dimethyl-2′E, 7′-octadienyloxy) coumarin (1), auraptene (2), umbelliferone (3), and xanthotoxin (4), as active compounds along with an inactive alkaloid, skimmianine (5). Compounds1 and2 inhibited MAO activity in a concentration-dependent manner with IC50 values of 0.7 and 1.7 μM, respectively. Compounds1 and2 showed a slight and potently selective inhibitory effect against MAO-B (IC50 0.5 and 0.6 μM, respectively) compared to MAO-A (IC50 1.3 and 34.6 μM, respectively). According to kinetic analyses derived by Lineweaver-Burk reciprocal plots, compounds1 and2 exhibited a competitive inhibition to MAO-B.

Protection of prenylated flavonoids from mori cortex radicis (Moraceae) against nitric oxide-induced cell death in neuroblastoma SH-SY5Y cells

Seven prenylated flavanoids, licoflavone C (1), cyclomulberrin (2), neocyclomorusin (3), sanggenon I (4), morusin (5), kuwanon U (6) and kuwanon E (7), and three 2-arylbenzofurans, moracin P (8), moracin O (9), and mulberrofuran Q (10) were isolated from the MeOH extract of Mori Cortex Radicis. Among these, compounds 2–7 enhanced cell viability in a dose-dependent manner against sodium nitroprusside-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay (EC50 values of 4.4, 5.6, 8.0, 6.4, 8.7, and 11.9 μg/mL, respectively). Among 10 compounds, C-3 prenylated flavones (2, 3, and 5) and prenylated flavanones (4, 6, and 7) showed cell protection. However, compound 1 which lacks the prenyl group at C-3 and three 2-arylbenzofurans (8–10) did not show protective effect. The order of cell protection was as follow: C-3 prenylated flavones (2, 3, and 5) > prenylated flavanones (4, 6, and 7) > 2-arylbenzofurans (8–10) and flavone (1). From this result, we show that some prenylated flavones and flavanones might protect neuronal cells against nitrosative stress-mediated cell death. Even though further evaluations are necessary in vitro and in vivo study, we carefully suggest that some prenylated flavonoids from Mori Cortex Radicis might protect neuronal cells from neurodegenerative diseases.

Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase

We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P. longum. Activity-guided fractionation of a methylene chloride soluble extract led to the isolation of three known piperine-related compounds, methylpiperate (1), guineensine (2), and piperlonguminine (3). Of these, methylpiperate (1) and guineensine (2) showed significant MAO inhibitory activities with IC50 values of 3.6 and 139.2 μM, respectively. Furthermore, methylpiperate (1) exhibited a selective inhibitory effect against MAO-B (IC50 value: 1.6 μM) than MAO-A (IC50 value: 27.1 μM). The kinetic study using the Lineweaver-Burk plots analysis suggested that methylpiperate (1) competitively inhibits MAO-A and MAO-B activities with the Ki values of 23.5 and 1.3 μM, respectively.

Inhibitory constituents of Nardostachys chinensis on nitric oxide production in RAW 264.7 macrophages

The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4α,5-dimethyl-1,3-dioxo-1,2,3,4,4α,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.6-21.6 μM.

Bioactive triterpenoids from Callistemon lanceolatus.

A new triterpenoid, 30-hydroxyalphitolic acid 1, and eight known triterpenoids, alphitolic acid 2, lupenol 3, 3-acetoxy-olean-18-en-28-oic acid 4, betulinic acid 5, ursolic acid 6, betulinic acid 3-O-caffeate 7, morolic acid 3-O-caffeate 8, and ursolic acid 3-O-caffeate 9, were isolated from Callistemon lanceolatus. Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. All compounds were evaluated for the inhibition of LPS-induced nitric oxide production in murine macrophage RAW264.7 cells. Betulinic acid 3-O-caffeate 7 showed a moderate inhibitory effect on nitric oxide production with IC50 value of 15.4 μM.