Lanostane triterpenoids from <Emphasis Type="Italic">Fomitopsis officinalis</Emphasis> and their trypanocidal activity

Fomitopsis officinalis is a medicinal fungus, known as ‘Agarikon’, and is used traditionally in the treatment of asthma and rheumatism in Mongolia. The investigation of the chemical constituents of F. officinalis led to the isolation of 4 new lanostane triterpenoids together with 4 known triterpenoids. Inhibitory activity against Trypanosoma congolense, which causes fatal diseases in animals including livestock, was estimated for the isolated compounds. Compounds 2–5 and 8 exhibited moderate inhibition activities with IC₅₀ values ranging from 7.0?27.1 µM.     

New triterpenoids from <Emphasis Type="Italic">Staphylea bumalda</Emphasis> flower buds and their neuroprotective activity against H<Subscript>2</Subscript>O<Subscript>2</Subscript>-induced injury in vitro

Four new acylated triterpene glycosides with aliphatic chains (4–7) as well as five known triterpenoids were isolated from the flower buds of Staphylea bumalda with bioassay guidance. Their structures were determined on the basis of spectral techniques, including IR, 1D and 2D NMR, and HR-APCI-MS. Most compounds (except 8) were isolated from S. bumalda for the first time. Additionally, the neuroprotective effects of 1 and 4–9 on suckling rat primary cultured hippocampal neurons against H₂O₂-induced injury were evaluated in vitro. The four new triterpenoids (4–7) showed neuroprotective effects, which increased the cell viability to over 74% at different concentrations, which was higher than the negative control (59%), while compounds 1 and 8–9 exhibited cytotoxic activity.     

Chemical constituents from <Emphasis Type="Italic">Viburnum fordiae</Emphasis> Hance and their anti-inflammatory and antioxidant activities

Three new neolignans, fordianoles A-C (1–3), characterized as (7S,8R)-4-hydroxy-3,3′,5′-trimethoxy-8′,9′-dinor-8,4′-oxyneolignan-7,7′,9-triol, (7R,8R)-4-hydroxy-3,3′,5′-trimethoxy-8′,9′-dinor-8,4′-oxyneolignan-7,7′,9-triol, and (7R,8R)-4-hydroxy-3,3′,5′-trimethoxy-8,4′-oxyneolignan-7,9,9′-triol-7′-one, together with an unusual γ-lactone, 3-(3,4-dihydroxyphenyl)-4-pentanolide (4), and twenty-five known compounds (5–29) were isolated from the aerial parts of Viburnum fordiae Hance. Their structures including absolute configurations were determined by spectroscopic and chemical methods. Among them, compounds 6, 7, 11–15, 17–28 were isolated from the Viburnum genus for the first time. The anti-inflammatory and antioxidant activities of all compounds were evaluated in vitro. Compounds 15, 19, 20 and 29 showed significant inhibitory activity on NO production in RAW264.7 cells stimulated by LPS with IC₅₀ values ranging from 8.60 to 13.92 μM. Meanwhile, compounds 1–4, 15, 19, 20, 22, 23, 25, 26 and 29 exhibited varying antioxidant activities through DPPH, ABTS free radical scavenging and FRAP assays.     

New ursane triterpenoids from <Emphasis Type="Italic">Ficus pandurata</Emphasis> and their binding affinity for human cannabinoid and opioid receptors

Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1β-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3β-acetoxy-20-taraxasten-22-one (3), 3β-acetoxy-11α-methoxy-olean-12-ene (4), 3β-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-β-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), β-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3β,21β-dihydroxy-11α-methoxy-olean-12-ene (16), 3β-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3β-acetoxy-urs-12-ene (21), and β-sitosterol-3-O-β-d-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D (¹H and ¹³C), 2D (¹H–¹H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.     

C<Subscript>21</Subscript> steroid derivatives from the Dai herbal medicine Dai-Bai-Jie,the dried roots of <Emphasis Type="Italic">Marsdenia tenacissima</Emphasis>, and their screening for anti-HIV activity

Twenty-three new C₂₁ steroidal glycosides, marstenacissides C1–C10 (1–10), D1–D7 (11–17) and E1–E6 (18–23), and four new C₂₁ steroids, 11α,12β-O-ditigloyl-tenacigenin C (24), 11α-O-benzoyl-12β-O-tigloyl-tenacigenin C (25), 11α-O-tigloyl-12β-O-benzoyl-tenacigenin C (26) and 11α-O-tigloyl-12β-O-benzoyl-marsdenin (27), were isolated from the Dai herbal medicine Dai-Bai-Jie, derived from the roots of Marsdenia tenacissima. The chemical structures of all compounds were established by spectroscopic techniques, including high-resolution mass spectrometry and NMR spectroscopy, as well as by comparison with reported spectral data. The anti-HIV activities of these compounds were screened, and the compounds obtained displayed inhibitory effects against HIV-1 with inhibition rates of 36.4–81.3% at 30 μM.     

Anti-inflammatory activity of compounds from the rhizome of <Emphasis Type="Italic">Cnidium officinale</Emphasis>

Five new compounds, 9,3′-dimethoxyhierochin A (1), 6-oxo-trans-neocnidilide (2), (±)-(3E)-trans-6-hydroxy-7-methoxydihydroligustilide (3), (±)-cnidiumin (4), and 6-(1-oxopentyl)-salicylic acid methyl ester (5), together with twenty known compounds (6–25), were isolated from the rhizome of Cnidium officinale. The chemical structures of new compounds were established by NMR spectroscopic techniques, mass spectrometry, Mosher’s method, and CD spectrum. Their anti-inflammatory activities were evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264.7 cells. Compounds 7, 13, and 14 showed inhibitory effects with IC₅₀ values of 5.1, 24.5, and 27.8 μM, respectively. In addition, compounds 7, 13, and 14 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression and cyclooxygenase-2 (COX-2) protein in a concentration-dependent manner.     

Two new ursane-type triterpenoid saponins from <Emphasis Type="Italic">Elsholtzia bodinieri</Emphasis>

Two new ursane-type triterpenoid saponins, bodiniosides M (1) and N (2), along with three known saponins, oblonganosides I (3), pseudobuxussaponin B (4) and bodinioside A (5), were isolated from the aerial parts of Elsholtzia bodinieri. The structures of compounds 1 and 2 were characterized by spectroscopic data as well as acid hydrolysis and GC analysis as 3-O-β-d-xylopyranosyl-19α-hydroxy-23-acetoxy-urs-12(13)-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1-2)-β-d-glucopyranoside and 3-O-β-d-glucopyranosyl-2α,19α-dihydroxy-urs-12(13)-en-28,20β-lactone. Compounds 1 and 5 exhibited potent anti-HCV activities in vitro with a selective index of 6.53 and 4.41, respectively.     

Synthesis and neuroprotective evaluation of (<Emphasis Type="Italic">E</Emphasis>)-3,4-dihydroxystyryl <Emphasis Type="Italic">p</Emphasis>-substituted-phenethyl ketone derivatives against inflammatory and oxidative injury

(E)-3,4-dihydroxystyryl p-substituted-phenethyl ketones and their 3,4-diacetylated derivatives were synthesized and examined their neuroprotective activities to further study the effect of p-substituents on the aromatic ring. The results revealed that steric hindrance effect of p-substituents has impact on neuroprotective activities against inflammatory and oxidative injury. Introduction of the bulkier groups are more beneficial to improve the neuroprotective activities than smaller groups. Compounds (4–5h, 4–5i and 4–5e) with p-substituted trifluoromethyl, isopropyl and t-butyl groups exhibited the best effects among all the target compounds.     

Two new naphthalenic lactone glycosides from <Emphasis Type="Italic">Cassia obtusifolia</Emphasis> L. seeds

Two new naphthalenic lactone glycosides, (3S)-9,10-dihydroxy-7-methoxy-3-methyl-1-oxo-3,4-dihydro-1H-benzo[g]isochromene-3-carboxylic acid 9-O-β-d-glucopyranoside (1) and (3R)-cassialactone 9-O-β-d-glucopyranoside (2) were isolated from seeds of Cassia obtusifolia Linn., along with five known compounds: (3R)-cassialactone 9-O-β-d-gentiobioside (3), emodin 1-O-β-gentiobioside (4), 1-hydroxyl-2-acetyl-3,8-dimethoxy-naphthalene 6-O-β-d-apiofuranosyl-(1?→?2)-β-d-glucopyranoside (5), rubrofusarin 6-O-β-d-gentiobioside (6), rubrofusarin 6-O-β-d-triglucoside (7). Structures of 1 and 2 were elucidated by NMR and HR-ESI-MS spectroscopic analysis. Their stereochemistry was determined by CD experiment. All compounds were tested for their ability to inhibit the formation of advanced glycation end-products in vitro. Compounds 1, 2, 3, 5, and 6 showed significant in vitro inhibitory activities (IC₅₀ values of 11.63, 23.40, 7.32, 89.03, and 38.89 µM, respectively).     

Alkyl phenols,alkenyl cyclohexenones and other phytochemical constituents from <Emphasis Type="Italic">Lannea rivae</Emphasis> (chiov) Sacleux (Anacardiaceae) and their bioactivity

Six novel compounds, 3-nonadec-14′-(Z)-enyl phenol (1a); 4,5-dihydroxy-4,2′-epoxy-5-[16′-Z-18′-E-heneicosenyldiene]-cyclohex-2-enone (2), 2,4,5-trihydroxy-2-[16′-Z-heneicosenyl]-cyclohexanone (3); 4S,6R-dihydroxy-6-[12′-Z-heptadecenyl]-cyclohex-2-enone (4a); 4S,6R-dihydroxy-6-[14′-Z-nonadecenyl]-cyclohex-2-enone (4b); and 1,2,4-trihydroxy-4-[16′-Z-heneicosenyl]-cyclohexane (5) were identified from the roots and stems of Lannea rivae in addition to the known cardanols, 3-heptadec-12′-Z-enyl phenol (1b), 3-pentadec-10′-Z-enyl phenol (1c) and 3-pentadecyl phenol (1d), sitosterol (6), sitosterol glucoside (7), taraxerone (8), taraxerol (9), E-lutein (10), myricetin (11), myricetin-3-O-α-rhamnopyranoside (12), myricetin-3-O-β-galactopyranoside (13) and (-)-epicatechin-3-O-gallate (14). The ketones 4a and 4b were isolated as a mixture and were qualitatively separated and identified by GCMS. Myricetin (11) and epicatechin gallate (14) displayed over 90 % DPPH radical-scavenging activity at 50 μg mL^?1, while its glycosides (12 and 13) showed percentages of over 70 % in the same assay. The same compounds 11 and 14 showed antibacterial activity similar to erythromycin and vancomycin against Gram-positive bacteria and were also active against Gram-negative bacteria, but not as much as the cefuroxime, ciprofloxacin and nalidixic acid standards. Compounds 1a–d, 4a–b and 5 were all relatively non-toxic, while 2 (the epoxy cyclohex-2-enone) and 3 (the trihydroxy cyclohexanone) showed more toxicity than the others. These two toxic compounds, 2 and 3 also showed antiplasmodial activity with IC₅₀ values between 0.48 and 2.05 μg mL^?1. The mixture of dihydroxy cyclohex-2-enones 4a and 4b, which was far less toxic than 2 and 3, also showed promising antiplasmodial activity and may be a possible lead for further investigation as an antiplasmodial drug.     

Design,synthesis, and evaluation of the anticonvulsant and antidepressant activities of pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine derivatives

A series of pyrido[2,3-d]pyrimidine derivatives (4a–4n, 5a–5n, 6, and 7) were designed and synthesized as potential anticonvulsants and antidepressants. Their pharmacological activities were evaluated by maximal electroshock test, forced swimming test, and tail suspension test in mice. Pharmacological analyses showed that compounds 4-benzyl-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4a) and 4-(3-fluorobenzyl)-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4e) exhibited the greatest anticonvulsant activity (PI 12.02 and 12.25, respectively, 30 min after intraperitoneal injection), and were more efficient than the reference drug, carbamazepine. In addition, 4-(4-fluorobenzyl)-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4f) and 6-(4-fluorobenzyl)-2,4-dimethylpyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(6H)-one (5f) possessed potent antidepressant properties that lead to significant reduction in the duration of the immobility time than did the control (P < 0.001), which possessed activities similar to those of fluoxetine. 4f showed obvious antidepressant activity at doses of 10 mg/kg.     

New phenylpropanoids from <Emphasis Type="Italic">Bulbophyllum retusiusculum</Emphasis>

Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum. The absolute configurations of the new compounds were determined by calculating their electronic circular dichroism (ECD), spectra and specific optical rotations and comparing the calculated values with the experimental data. Compound 2 exhibited potent antifungal activity against Candida albicans (16 μg/mL). Compound 3 showed moderate antibacterial activity against Bacillus subtilis (64 μg/mL).     

Chemical structures of constituents from the leaves of <Emphasis Type="Italic">Polyscias balfouriana</Emphasis>

A new pyrrolidine derivative, (5S)-hydroxyethyl 2-oxopyrrolidine-5-carboxylate (1), a new flavonol glycoside, tamaraxetin 3,7-di-O-α-l-rhamnopyranoside (2), and a new triterpene saponin, polyscioside A methyl ester (3), along with six known compounds (4–9) were isolated from the leaves of Polyscias balfouriana. Their chemical structures were elucidated on the basis of extensive spectroscopic analysis.     

Phenylacylphenol derivatives with anti-melanogenic activity from <Emphasis Type="Italic">Stewartia pseudocamellia</Emphasis>

Three new phenylacylphenol derivatives, stewartianol (1), deoxystewartianol-4′-O-arabinoglucoside (2), and stewartianol-3-O-glucoside (3), along with nine known compounds, methylesculin (4), fraxoside (5), fraxetin (6), scopletin (7), (+)-dihydromyricetin (8), (+)-taxifolin-7-O-β-d-glucose (9), (+)-taxifolin (10), (+)-dihydrokaempferol-7-O-β-d-glucose (11), and 3-acetyl-ursolic acid (12), were isolated from the twigs of Stewartia pseudocamellia; commonly used as folk medicine in Korea. The structures of the isolated compounds were identified using spectroscopic analysis, including 1D, 2D NMR, MS and compared with published data. The compounds were tested for their anti-melanogenic activity in cultured murine B16 melanoma cells. Stewartianol (1) and stewartianol-3-O-glucoside (3) showed an inhibitory effect significantly on melanogenesis in a concentration-dependent manner.     

Antioxidant <Emphasis Type="Italic">C</Emphasis>-glycosylflavones of <Emphasis Type="Italic">Drymaria cordata</Emphasis> (Linn.) Willd

A new C-glycosylflavone, drymaritin E (6-C-(3-keto-β-digitoxopyranosyl)-4′-O-(β-d-glucopyranosyl)-7-methoxyl-5,4′-dihydroxylflavone) 1 was isolated from the oily upper phase (SU) of the MeOH extract from aerial parts of Drymaria cordata together with two known compounds (cassiaoccidentalin A 2 and anemonin 3) and an inseparable mixture of two known C-glycosylflavones 5,4′-dihydroxy-7-methoxyflavone-6-C-(2′′-O-α-l-rhamnopyranosyl)-β-d-glucopyranoside 4a and 5,7,3′,4′-tetrahydroxyflavone-6-C-(2′′-O-α-l-rhamnopyranosyl)-β-d-glucopyranoside 4b. The alkaline hydrolysis of 3 led to a new hemisynthetic derivative, sodium anemonate (sodium 2-((1’E) 2′-sodium-carboxylate-vinyl)-5-oxo-cyclohex-1-ene carboxylate) 3a. The chemical structures were determined by spectroscopic methods (¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMBC, HSQC, and NOESY) and mass spectrometry (ESI–MS). C-glycosylflavones had significant free radical-scavenging activities on the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). However, SU and compounds 3 and 3a exhibited no activity. In particular, compound 1 exhibited a concentration-dependent radical scavenging activity on DPPH with EC₅₀ of 31.43 µg/mL.     

Synthesis,antimicrobial and nematicidal evaluation of a new class of triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]quinazolinylthiazolidinones

In an attempt to find a new class of antimicrobial and nematicidal agents, a series of 2-aryl/heteryl-3-(5-phenyl[1,2,4]triazolo[4,3-c]quinazolin-3-yl)-1,3-thiazolidin-4-ones 5a-k was prepared by one-pot three-component reaction, involving 5-phenyl[1,2,4]triazolo[4,3-c]quinazolin-3-amine 4, aryl/heteroaryl aldehydes and thioglycolic acid, and characterized by physicochemical as well as spectral means. All the newly synthesized compounds 5a–k were tested in vitro for their antimicrobial activity against three representative Gram-positive (Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus), Gram-negative (Proteus vulgaris, Salmonella typhimurium, Escherichia coli) bacteria and four fungal strains (Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, Trichophyton mentagrophytes). These compounds 5a–k, were also evaluated for their nematicidal activity against two nematodes (Ditylenchus myceliophagus, Caenorhabditis elegans). Except phenyl substituted, all the ten aryl/heteroaryl substituted compounds 5b–k showed significant antimicrobial and nematicidal properties against tested microorganisms. Particularly, compounds 5b, 5c, 5g, 5h, 5j and 5k containing electron-withdrawing substituents like chlorophenyl, nitrophenyl, furyl and 1,3-benzodioxole exhibited promising activity comparable to employed standards Ampicillin, Amphotericin B and Levamisole, and emerged as potent antimicrobial and nematicidal agents.     

Anti-oral common pathogenic bacterial active acetylenic acids from <Emphasis Type="Italic">Thesium chinense</Emphasis> Turcz

Discovery of agents for oral infectious diseases is always encouraged in natural products chemistry. A bioassay-guided isolation led to the isolation of two new acetylenic acids (1, 2) along with seven known ones (3–9) from the ethanol extract of Thesium chinense Turcz, a commonly used oral anti-bacterial and anti-inflammatory herb. Their structures were elucidated on the basis of spectroscopic and chemical evidence. Exocarpic acid (3) demonstrated the most promising activity against three tested oral pathogenic bacterial strains, Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans, with minimum inhibitory concentration values of 0.86, 3.43, and 13.70 μg/mL, respectively. Compounds 1, 2, 4, 5 and 7 also showed potential activities against periodontal bacteria (P. gingivalis, F. nucleatum).     

Identification of <Emphasis Type="Italic">N</Emphasis>-arylsulfonylpyrimidones as anticancer agents

For confirming the role of five membered ring of imidazolidinone moiety of N-arylsulfonylimidazolidinones (7) previously reported with highly potent anticancer agent, a series of N-arylsulfonylpyrimidones (10a–g) and N-arylsulfonyltetrahydropyrimidones (11a–e) were prepared and their anti-proliferating activity was measured against human cancer cell lines (renal ACHN, colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3) using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4-phenyltetrahydropyrimidin-2(1H)-one (11d, mean GI₅₀ = 3.50 µM) and ethyl 5-(2-oxo-4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean GI₅₀ = 0.26 µM) showed best growth inhibitory activity against human cancer cell lines. Considering the activity results, N-arylsulfonyltetrahydropyrimidones (11) exhibited more potent activity compared to N-arylsulfonylpyrimidones (10) and comparable activity to N-arylsulfonylimidazolidinones (7). Especially, tetrahydropyrimidin-2(1H)-one analogs containing acylindolin-5-ylsulfonyl moiety at position 1 demonstrated their strong growth inhibitory activity against human cancer cell lines.     

In vitro cytotoxic activity of isolated compounds from Malaysian <Emphasis Type="Italic">Calophyllum</Emphasis> species

Cancer is a leading cause of death worldwide. In our continuing search for new anticancer agents, four Malaysian Calophyllum species, namely C. castaneum, C. teysmannii, C. canum, and C. sclerophyllum, had been phytochemically studied to give compounds 1–12. All the isolated compounds were evaluated for their antiproliferative activity against nasopharyngeal (SUNE1, TW01, CNE1, HK1) and breast (HCC38, MDA-MB-231, MDA-MB-468, SKBR3) cancer cell lines via methyl thiazolyl tetrazolium cell viability assay. Among the tested compounds, isodispar B (1) showed a promising dose-dependent and a broad spectrum of cytotoxic effects on all the tested cancer cell lines; in particular, potent inhibitory activities were observed on nasopharyngeal cancer cell lines (SUNE1, TW01, CNE1, HK1), with IC₅₀ values ranging from 3.8 to 11.5 µM. In comparison with 5-fluorouracil as positive control, compound 1 was found to exhibit at least sixfold much higher activity than the standard drug used against the nasopharyngeal cell lines. Compound 1 was later found to induce apoptotic cell death in nasopharyngeal cancer cells, as evidenced by ‘Cell Death Detection’ ELISA^PLUS kit, and exhibited good cancer-specific cytotoxicity when tested with noncancerous NP460 cells. Meanwhile, compounds 2–12 displayed moderate to weak activities against the tested cancer cell lines. The findings have highlighted the therapeutic potential of compound 1 against nasopharyngeal cancer.     

Identification of cytoprotective constituents of the flower buds of <Emphasis Type="Italic">Tussilago farfara</Emphasis> against glucose oxidase-induced oxidative stress in mouse fibroblast NIH3T3 cells and human keratinocyte HaCaT cells

A new cytoprotective compound, 1-[(4S)-3,4-dihydro-4-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl]-ethanone (1) was isolated from the flower buds of Tussilago farfara L. (Compositae), together with eight known compounds, 3,4-dicaffeoyl isoquinic acid (2), trans-cinnamic acid (3), 4-hydroxyacetophenone (4), 4,5-dicaffeoylquinic acid methyl ester (5), 3,5-dicaffeoylquinic acid methyl ester (6), 4-hydroxybenzoic acid (7), isoquercetrin (8), and ligucyperonol (9). Compounds 2–4 were found in this plant for the first time. The isolates 1–9, were tested for their cytoprotective activities against glucose oxidase-induced oxidative stress in mouse fibroblast NIH3T3 cells and human keratinocyte HaCaT cells. Among them, 1 and 3 showed significant cytoprotective activities as determined by MTT assay and lactate dehydrogenase leakage, indicating their possibility as the potent cytoprotective agents. The structure of 1 was determined by spectroscopic data analysis including 1D- and 2D-NMR experiments, and its absolute configuration was elucidated by a circular dichroism.