Anthraquinones from the Roots of <Emphasis Type="Italic">Knoxia valerianoides</Emphasis> inhibit the formation of advanced glycation end products and rat lens aldose reductase <Emphasis Type="Italic">in vitro</Emphasis>

Eight known compounds, lucidin (1), lucidin-ω-methyl ether (2), rubiadin (3), damnacanthol (4), 1,3,6-trihydroxy-2-methoxymethylanthraquinone (5), 3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (6), 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone 3-O-β-primeveroside (7), and vanillic acid (8), were isolated from EtOAc- and n-BuOH-soluble fractions of the roots of Knoxia valerianoides. The structures of 1–8 were identified by analysis of spectroscopic data as well as by comparison with published values. All the isolates were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. Compound 5 showed the most potent inhibitory activity (IC₅₀ = 52.72 μM) against AGEs formation. Compounds 1, 2, and 8 also showed potent inhibitory activity on AGEs formation with IC₅₀ values of 79.28, 62.79, and 93.93 μM, respectively, compared with positive control, aminoguanidine (IC₅₀ = 962 μM). While, compounds 1 and 5–7 showed strong inhibitory activity against RLAR with IC₅₀ values of 3.35, 3.04, 6.39, and 2.05 μM, respectively.     

Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from <Emphasis Type="Italic">Ulmus davidiana</Emphasis> var. <Emphasis Type="Italic">japonica</Emphasis>

Twenty five compounds including ten triterpenes (1–3, 5–11), six flavonoids (12–15, 24, 25), five lignans (17, 18, 21–23), two butenyl clohexnone glycosides (19–20), one fructofuranoside (16) and one fatty acid (4) were isolated from the roots of Ulmus davidiana var. japonica. The structures of those compounds were identified by comparing their physicochemical and spectral data with those of published in literatures. All the compounds were evaluated for DNA topoisomerase inhibitory activities and cytotoxicities. Among the purified compounds, 4 and 19 showed more potent inhibitory acitivities (IC₅₀: 39 and 19 μM, respectively) than camptothecin, as the positive control (IC₅₀: 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC₅₀: 0.1, 0.52, 0.47, 0.42, 0.17 μM and 17 nM, respectively), which were more potent than that of etoposide as positive control (IC₅₀: 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC₅₀: 4 μM and 3 μM, respectively, with IC₅₀ of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC₅₀: 4, 3 and 4 μM, respectively, with IC₅₀ of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC₅₀: 19, 19 and 15 μM, respectively, with IC₅₀ of camptothecin: 2 μM).     

Cholinesterase inhibitors from <Emphasis Type="Italic">Cleistocalyx operculatus</Emphasis> buds

Five flavonoids, myricetin-3′-methylether 3-O-β-d-galactopyranoside (1), myricetin-3′,5′-dimethylether 3-O-β-d-galactopyranoside (2), quercetin (3), kaempferol (4), and tamarixetin (5) were isolated from the buds of Cleistocalyx operculatus (Myrtaceae). The chemical structures of these compounds were determined on the basis of spectroscopic analyses, including 2D NMR. Their anti-Alzheimer effects were evaluated via acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity assays. All five compounds 1–5 showed potential inhibitory activities against AChE with IC₅₀ values of 19.9, 37.8, 25.9, 30.4 and 22.3 μM, respectively, while compounds 1, 3, 4 and 5 also possessed BChE inhibitory activity with IC₅₀ values of 152.5, 177.8, 62.5, and 160.6 μM, respectively.     

Bioassay-guided isolation of fatty acid synthase inhibitory diterpenoids from the roots of <Emphasis Type="Italic">Salvia miltiorrhiza</Emphasis> Bunge

Fatty acid synthase (FAS) is considered as a novel drug target for the development of anticancer and anti-obesity agents. Bioassay-guided fractionation of a n-hexane-soluble extract prepared from the roots of Salvia miltiorrhiza Bunge (Labiatae), using an in vitro enzyme assay, led to the isolation of five abietane diterpenoids: 15,16-dihydrotanshinone I (1), cryptotanshinone (2), tanshinone I (3), tanshinone IIA (4), and dansenspiroketallactone (5). Compounds 1–5 were tested for their in vitro FAS inhibitory activity and, except for compound 5 (IC₅₀ > 100 μM), compounds 1–4 inhibited the enzyme activity with IC₅₀ values ranging from 12.0 to 30.3 μM. Our findings may be partially related to the anticancer activity of abietane diterpenoids from the plant, suggesting a further study on the anticancer potential of tanshinone derivatives.     

Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1<Emphasis Type="Italic">H</Emphasis>-benzimidazole derivatives as potential anticancer agents

In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1–6) as potential anticancer agents. Cytotoxicity was evaluated against seven human neoplastic cell lines using the MTT assay. Compound 6 [2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole] was the most active of the series, showing an IC₅₀ of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC₅₀ = 22.2 μM). Compounds 3 and 6 induce arrest in the S phase of the cell cycle, and compounds 1–6 induce apoptosis in the K562 cell line. Compound 6 induces poly (ADP-ribose) polymerase (PARP) inhibition activity as a potential mechanism of action. These results suggest that compound 6 could be a potent anticancer agent. Compound 3 displayed the best inhibitory activity against PARP with an IC₅₀ value of 0.05 μM, compared to the activity shown by the positive control 3-aminobenzamide (IC₅₀ = 28.5 μM).     

<Emphasis Type="Italic">In vitro</Emphasis> sortase a inhibitory and antimicrobial activity of flavonoids isolated from the roots of <Emphasis Type="Italic">Sophora flavescens</Emphasis>

A series of flavonoids (1–14) was isolated from the roots of Sophora flavescens. We evaluated their ability to inhibit both microbial growth and sortase A, an enzyme that plays a key role in cell wall protein anchoring and virulence in Staphylococcus aureus. Most prenylated flavonoids (7–13) displayed potent inhibitory activity against gram-positive and gram-negative bacteria except E. coli, with minimum inhibitory concentrations values ranging from 4.40 to 27.7 μM, and weak or no activity against fungal strains tested. Kurarinol (6) was a potent inhibitor of sortase A, with an IC₅₀ value of 107.7 ± 6.6 μM. A preliminary structure-activity relationship, including essential structural requirements, is described.     

Constituents of cultivated <Emphasis Type="Italic">Agaricus blazei</Emphasis>

Two phenylhexane derivatives (1, 2), benzoylergostane (3), N-benzoyl-l-leucine methyl ester (4), two known ergostanes, and highly degraded incisterol were isolated from fruit bodies of Agaricus blazei. Compound 3 exhibited strong cytotoxicity toward HepG2 cells (IC₅₀ = 6.0 ± 0.33 μM).     

Cytotoxic lasiodiplodin derivatives from the fungus <Emphasis Type="Italic">Syncephalastrum racemosum</Emphasis>

Chemical investigation of fungal biomass of the fungus Syncephalastrum racemosum led to the isolation of new natural products (3R),(5S)-5-hydroxy-de-O-methyllasiodiplodin (1), 6-oxode-O-methyllasiodiplodin (2), in addition to five known compounds, de-O-methyllasiodiplodin (3), lasiodiplodin (4), (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin (5), ergosterol (6), and ergosterol peroxide (7). Their structures were elucidated by spectroscopic techniques. The absolute configuration of 1 was determined by a modified Mosher’s method. Compound 1 showed cytotoxicity against cholangiocarcinoma, KKU-M139, KKU-M156, and KKU-M213 cell lines with IC₅₀ values in the range of 14–19 μg/mL, while 3 showed cytotoxicity against KB, BC1, and NCI-H187 cell lines with IC₅₀ values of 12.67, 9.65, and 11.07 μg/mL, respectively.     

Two acetylated megastigmane glycosides from the leaves of <Emphasis Type="Italic">Ilex paraguariensis</Emphasis>

Two acetylated megastigmane glycosides, matenosides A (1) and B (2), have been isolated from the MeOH extract of Ilex paraguariensis leaves, and their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 exhibited human neutrophil elastase (HNE) inhibitory activity with IC₅₀ values of 50.4 μM and 11.1 μM, respectively.     

Biological activity of chemical constituents from <Emphasis Type="Italic">Clausena harmandiana</Emphasis>

The activity guided fractionation of the Clausena harmandiana root extracts led to the isolation of a coumarin, a ferulate, and eight carbazoles. This is the first report of the isolation of compounds 2–4 and 6–10 from this species, and this is the first time 10 was isolated from this genus. Compound 4 showed strong cytotoxicity against NCI-H187 cells with an IC₅₀ value of 1.63 μg/mL. Compound 5 demonstrated strong cytotoxicity against MCF-7 and KB cell lines with IC50 values of 2.21 and 1.74 μg/mL, respectively. Compounds 3 and 4 exhibited moderate cytotoxicity against the MCF-7 cell line, and 8 showed moderate cytotoxicity against NCIH187 and KB cell lines. Compounds 3 and 5 showed antiplasmodial activity with IC₅₀ values of 3.27 and 2.94 μg/mL, respectively.     

Triterpenoid saponins from the seeds of <Emphasis Type="Italic">Caragana microphylla</Emphasis>

Two new triterpenoid saponins, namely caraganoside C (1) and caraganoside D (2), were isolated from the seeds of Caragana microphylla. Their structures were elucidated on the basis of spectroscopic analyses, including homo- and hetero-nuclear correlation NMR experiments (COSY, HSQC and HMBC). Both 1 and 2 exhibited moderate inhibitory activity against NO production in LPS-stimulated RAW264.7 cells with IC₅₀ values of 26.4 μM and 32.2 μM, respectively. In addition, 1 showed weak cytotoxicity against MCF-7, HL-60, HCT116, and A549 cell lines.     

Solalyratins A and B,new anti-inflammatory metabolites from <Emphasis Type="Italic">Solanum lyratum</Emphasis>

A new coumestan (solalyratin A, 1) and a novel cyclic eight-membered α,β-unsaturated ketone (solalyratin B, 3), together with three known compounds, puerariafuran (2), coumestrol (4) and 9-hydroxy-2′,2′-dimethylpyrano[5′,6′:2,3]-coumestan (5), were isolated from the whole plant of Solanum lyratum. Their structures were elucidated on the basis of spectroscopic analyses. In vitro, compounds 1–5 showed anti-inflammatory activities, with IC₅₀ values in the range 6.3–9.1 μM.     

<Emphasis Type="Italic">In vitro</Emphasis> Na<Superscript>+</Superscript>/K<Superscript>+</Superscript>-ATPase inhibitory activity and antimicrobial activity of sesquiterpenes isolated from <Emphasis Type="Italic">Thujopsis dolabrata</Emphasis>

A series of sesquiterpenes and hinokitiol-related compounds (1–15) was isolated from the essential oil of Thujopsis dolabrata Sieb. et Zucc. var. hondai Makino, and their structures were determined by combined spectroscopic analyses. The inhibitory effects of these compounds on microbial cell growth and Na⁺/K⁺-ATPase were evaluated in vitro. It was found that (−)-elema-1,3,11(13)-trien-12-ol (5), α,β,γ-costol (8), and chamigrenol (11) inhibit the activities of Na⁺/K⁺-ATPase, with IC₅₀ values of 11.2 ± 0.11, 12.2 ± 0.09, and 15.9 ± 0.54 μg/mL, respectively. Thujopsene (1), cedrol (9), γ-cuparenol (10), and chamigrenol (11) showed potent antibacterial activity, with MIC values in the range of 25–50 μg/mL, and β-thujaplicin (12) exhibited a broad spectrum of antibacterial and antifungal activity. These results indicate that these isolated compounds are promising candidates for the development of potent Na⁺/K⁺ ATPase inhibitors and antimicrobial agents.     

Free radical scavenging and antielastase activities of flavonoids from the fruits of <Emphasis Type="Italic">Thuja orientalis</Emphasis>

Bioassay-guided fractionation of the MeOH extract of Thuja orientalis fruits using a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay led to the isolation of 9 flavonoids: cupressuflavone (1), amentoflavone (2), robustaflavone (3), afzelin (4), (+)-catechin (5), quercitrin (6), hypolaetin 7-O-β-xylopyranoside (7), isoquercitrin (8) and myricitrin (9). Their chemical structures were determined by spectroscopic analyses. The free radical scavenging and human neutrophil elastase (HNE) inhibitory activities were evaluated for the isolated compounds. By DPPH scavenging assay, compounds 5, 6, 7, 8 and 9 showed anti-oxidant activities with IC₅₀ values of 28.66, 31.19, 18.30, 26.63 and 15.10 μM, respectively. By ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt] scavenging assay, these compounds also exhibited potent anti-oxidant activities with IC₅₀ values of 6.77, 13.96, 6.97, 22.79 and 9.96 μM, respectively. Of note, compounds 1, 2 and 3 showed significant HNE inhibitory activities with IC₅₀ values of 8.09, 1.27 and 1.33 μM, respectively.     

Lignans from the flowers of <Emphasis Type="Italic">Osmanthus fragrans</Emphasis> var. <Emphasis Type="Italic">aurantiacus</Emphasis> and their inhibition effect on NO production

A new lignan, (7R,7′R,8R,8′R)-8-hydroxypinoresinol 8-O-β-D-glucopyranoside 4′-methyl ether (7), was isolated from the flowers of Osmanthus fragrans var. aurantiacus along with six known lignans: (+)-phillygenin (1), phillyrin (2), (−)-phillygenin (3), (−)-epipinoresinol-β-D-glucoside (4), taxiresinol (5), and (−)-olivil (6). The structure of the new compound was elucidated on the basis of 1D- and 2D-NMR spectroscopic analysis and specific rotation data. The compounds isolated from the flowers of O. fragrans var. aurantiacus were evaluated for inhibitory activities on nitric oxide production in lipopolysaccharide-stimulated macrophage RAW 264.7 cells. (+)-Phillygenin (1), phillyrin (2), and (−)-phillygenin (3) exerted the strongest inhibitory activities on NO production with IC₅₀ values of 25.5, 18.9, and 25.5 μM, respectively. These compounds may prove beneficial in the development of natural agents for prevention and treatment of inflammatory diseases.     

Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

Chemical constituents of <Emphasis Type="Italic">Melandrium firmum</Emphasis> Rohrbach and their anti-inflammatory activity

In our ongoing search for anti-inflammatory agents originating from Korean medicinal plants, we found that the hexane and BuOH fractions of the MeOH extract from the whole plants of Melandrium firmum Rohrbach inhibited 5-lipoxygenase (5-LOX) activity. By activity-guided fractionation, eleven compounds, α-spinaterol (1), ursolic acid (2), ergosterol peroxide (3), α-spinaterol glucoside (4), 2-methoxy-9-β-D-ribofuranosyl purine (5), aristeromycin (6), ecdysteron (7), polypodoaurein (8), (-)-bornesitol (9), mannitol (10) and cytisoside (11) were isolated from the hexane and BuOH fractions using column chromatography. Compounds 2, 5, 6, 8, 9, 10 and 11 were isolated for the first time from this plant. Compounds 1, 3, 4 and 7 inhibited 5-LOX activity with IC₅₀ values of 21.04 μM, 42.30 μM, 32.82 μM, and 17.18 μM, respectively. Ming Shan Zheng and Nam Kyung Hwang contributed equally to this work.     

A new furostanol saponin from <Emphasis Type="Italic">Asparagus cochinchinensis</Emphasis>

A new furostanol saponin, (25S)-26-O-β-d-glucopyranosyl-5β-furost-20(22)-en-3β, 15β,26-triol-3-O-[α-l-rhamnopyranosyl-(1–4)]-β-d-glucopyranoside, namely, aspacochioside D (1) were isolated from Asparagus cochinchinensis (Lour.) Merr, along with three known saponins, aspacochioside C (2), (25S)-5β-spirostan-3β-yl-O-[O-α-l-rhamnopyranosyl-(1–4)]-β-d-glucopyranoside (3), and pseudoprotoneodioscin (4). The structure of 1 was elucidated on the basis of chemical reactions and spectral analysis (IR, GC, ESI-MS, ¹H-NMR, ¹³C-NMR, DEPT, HMBC, HMQC and NOESY). The antiproliferative effects of 1–4 were evaluated in a cytotoxicity assay against the human tumor cell line, A549. Compound 2 (Aspacochioside C) exhibited moderate cytotoxicity against A-549, with an IC₅₀ value of 3.87 μg/mL.     

Cytotoxic 10-(indol-3-yl)-[13]cytochalasans from the fungus <Emphasis Type="Italic">Chaetomium elatum</Emphasis> ChE01

Nine 10-(indol-3-yl)-[13]cytochalasans such as a new chaetoglobosin V (1); two new natural products, prochaetoglobosin III (2) and prochaetoglobosin III_ed (3); six known chaetoglobosins B-D (4–6), F (7), and G (8) and isochaetoglobosin D (9) in addition to two known sterols, 24(R)-5α,8α-epidioxyergosta-6–22-diene-3β-ol (10) and ergosterol (11), were isolated from the fungus Chaetomium elatum ChE01. The structures of these compounds were elucidated by spectroscopic methods. Compounds 1–9 showed cytotoxicity against the human breast cancer (IC₅₀ 2.54–21.29 μM) and cholangiocarcinoma cell lines (IC₅₀ 3.41–86.95 μM).     

Cytotoxic constituents of<Emphasis Type="Italic">diadema setosum</Emphasis>

5,8-Epidioxycholest-6-en-3-ol (1), cholesterol (2), glycerol 1-palmitate (3) and glycerol 1,3-dioleate-2-stearate (4) were isolated from the methanol extract of the sea urchinDiadema setosum, which was collected from the Halong sea, Vietnam. Chemical structures were established based on extensive 1D, 2D-NMR, FAB-MS, EI-MS spectroscopic data and GC-MS analysis. The NMR spectral data of compound 1 were reassigned by using HMQC and HMBC. Compound1 was found to have strong cytotoxic effect against various cancer cell lines, such as KB (IC₅₀, 2.0 μg/mL), FL (IC₅₀, 3.93 μg/mL), and Hep-2 (IC₅₀, 2.4 μg/mL) byin vitro assay.