Aromatic acid derivatives from the lateral roots of Aconitum carmichaelii

Seven new aromatic acid derivatives (1–7), together with five known analogs, were isolated from the lateral roots of Aconitum carmichaelii. Structures of the new compounds were determined by spectroscopic and chemical methods as 4-methyl ( ? )-(R)-hydroxyeucomate (1), 4-butyl ( ? )-(R)-hydroxyeucomate (2), 4-butyl-1-methyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (3), 1-butyl-4-methyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (4), dimethyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (5), dimethyl (+)-(R)-2-O-(4′-hydroxybenzoyl)malate (6), and methyl ( ± )-3-(4′-hydroxy-3′-methoxyphenyl)-3-sulfopropionate (7), respectively. Compounds 1 and 2 are 2-benzylmalates (eucomate derivatives), 3–6 belong to 2-O-benzoylmalates, and 7 is a rare phenylpropionate containing a sulfonic acid group. The absolute configurations of eucomate derivatives were confirmed by X-ray crystallographic analysis of 4-methyl eucomate (11).     

Ceramides and cerebrosides from the marine bryozoan Bugula neritina inhabiting South China Sea

From the marine bryozoan Bugula neritina inhabiting South China Sea, a new ceramide named (2S,3R,4E)-2-(14′-methyl-pentadecanoylamino)-4-octadecene-l,3-diol (1) and a new cerebroside named 1-O-(β-d-glucopyranosyl)-(2S,3R,4E)-2-(heptadecanoylamino)-4-octadecene-l,3-diol (6), together with one known ceramide (2) and three known cerebrosides (3, 4, and 5), were isolated. Their structures were deduced by extensive spectral analysis and chemical evidences. Compound 1 is branched with a methyl [–CH(CH₃)₂] in the fatty acid moiety, which is a rare structural feature among ceramides. Compound 6 is a new cerebroside with 17 carbons in the fatty acid moiety, while 5 is a new natural product which was isolated from a natural origin for the first time.     

Two new aromatic compounds from the resin of Styrax tonkinensis (Pier.) Craib

Two new aromatic compounds, trans-(tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-5-oxofuran-3-yl)methyl benzoate (1), 3-(4-hydroxy-3-methoxyphenyl)-2-oxopropyl benzoate (2) and one new natural product, 4-((E)-3-ethoxyprop-1-enyl)-2-methoxyphenol (3) together with five known aromatic compounds have been isolated from the resin of Styrax tonkinensis (Pier.) Craib. Their structures were determined by physical and spectroscopic methods.     

Two novel flavanes from the leaves of Morus alba L.

Two new flavanes, (2R,4S)-2′,4′-dihydroxy-2H-furan-(3″,4″:8,7)-flavan-4-ol (1) and (2S)-2′,4′-dihydroxy-7-methoxyl-8-butyricflavane (2), together with four known flavonoids, were isolated from the leaves of Morus alba L. Their structures were determined on the basis of spectroscopic analysis.     

Bioassay-guided isolation of Poliovirus-inhibiting constituents from Zephyranthes candida

Abstract

Context: Plants of the Zephyranthes genus are globally used in folk medicine. In a previous study, Zephyranthes candida Linn. (Amaryllidaceae) was identified as having antiviral properties; this led to anti-poliovirus assay-guided isolation of compounds from crude methanol extract of the plant.

Objective: Isolation of anti-poliovirus constituents from Z. candida.

Material and methods: Active chloroform fraction from crude methanol extract of Z. candida (whole plant) was subjected to bioassay-guided fractionation; repeated column and preparative thin layer chromatography led to isolation of active compounds. Chemical structures were identified using spectroscopic techniques. Using serial two-fold dilution of maximum non-toxic concentration (MNTC) of each compound (0.0625–1?µg/mL for lycorine and 0.625–10?µg/mL for trisphaeridine and 7-hydroxy-3′,4′-methylenedioxyflavan), the ability of extracts to inhibit viral-induced cell death in tissue culture was evaluated 72?h post-infection by the colorimetric method using MTT (3-[4,5-dimethylthiazol–2-yl]-2,5-diphenyltetrazolium bromide) dye. Regression analysis was used to determine 50% inhibitory concentration (IC₅₀) and 50% cytotoxicity concentration (CC₅₀), from which selective index (SI) was calculated.

Results: From the chloroform fraction, three compounds were isolated and identified, namely lycorine (1), trisphaeridine (2), and 7-hydroxy-3′,4′-methylenedioxyflavan (3) as the anti-polioviral components. Lycorine was the most active, with an IC₅₀ value of 0.058?µg/mL followed by trisphaeridine (2) with an IC₅₀ of 0.1427?µg/mL, and 7-hydroxy-3′,4′-methylenedioxyflavan (3) with an IC₅₀ of 0.2384?µg/mL.

Discussions and conclusions: The antipoliovirus activity of trisphaeridine (2) and 7-hydroxy-3′,4′-methylenedioxyflavan (3) is established in this report; these compounds are of moderate toxicity and have very good SI. They could be a potential template for the development of a new antiviral agent.     

Structural elucidation of a new flavone from Sarcopyramis nepalensis

A novel flavone, named 4′-methoxy-3′,5,7-trihydroxy-8-(1″-(3?,4?,5?-trihydroxyphenyl)ethyl)flavone (1), was isolated from Sarcopyramis nepalensis, along with two known compounds syringaresinol (2) and aralidioside (3). Their structures were established by the spectroscopic analysis, especially by 2D NMR. All of the three compounds were isolated from the plant for the first time.     

Two new phenol derivatives from Stereum hirsutum FP-91666

Two new phenol derivatives, 2-(3-methyl-2-buten-1-yl)-4-methoxyethyl-phenol (1) and 5-hydroxy-4-(hydroxymethyl)-2-(3-methylbut-2-en-1-yl)cyclohex-4-en-1-one (2), together with eight known compounds consisting of phenol derivatives (3 and 4), niacinamide (5), and five ergosta type compounds (6–10), were isolated from solid fermentation products of Stereum hirsutum FP-91666. Two new structures were elucidated by extensive spectroscopic methods, including 1D NMR and 2D NMR, and HR-EI-MS experiments.     

Studies on the alkaloid constituents of Evodia rutaecarpa (Juss) Benth var. bodinaieri (Dode) Huang and their acute toxicity in mice

Six alkaloids (1–6) have been isolated from the fruits of Evodia rutaecarpa (Juss) Benth var. bodinaieri (Dode) Huang, two of which are new compounds, identified as 2-undecyl-4(1H)-quinolone (4) and 1-methyl-2-undecanone-10′-4(1H)-quinolone (5); the known compounds were identified as rutaecarpine (1), evodiamine (2), 1-methyl-2-undecyl-4(1H)-quinoline (3) and 2-undecanone-10′-4(1H)-quinolone (6). Compounds 1–5 were evaluated for their acute toxicity.     

Two new 8-O-4′-type lignans from the stem of Schima superba and their cell growth inhibitory activities against human cancer cell lines

Two new lignans (1 and 2) were isolated from the EtOH extracts of the stem of Schima superba, and elucidated as (7R,8S)-1-(3,4-dimethoxyphenyl)-2-O-(2-methoxy-4-omegahydroxypropylphenyl)propane-1,3-diol (1) and threo-1-(4-hydroxy-3-methoxyphenyl)-1-methoxy-2-{4-[1-formyl-(E)-vinyl]-2-methoxyphenoxy}-3-propanol (2) by spectral analysis. Compounds 1 and 2 showed cell growth inhibitory activity against HeLa, CNE, HepG-2, and HEp-2 cell lines. Compound 1 exhibited significant cytotoxicities with IC₅₀ values of less than 4 μg/ml against all the tested cell lines.     

Synthesis of higenamine,A cardiotonic principle of aconite root

Higenamine (I), a cardiotonic principle of Aconite root, was synthesized from 4-methoxy-phenylacetic acid (II) and β-(3, 4-dimethoxyphenyl)-ethylamine (IV). Condensation ofIV with 4-methoxyphenylacetyl chloride (III) was followed by cyclodehydration yielding 1-(4′-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline (VI). Reduction ofVI to 1, 2, 3, 4-tetrahydroisoquinoline (VII) and subsequent demethylation provided desired product higenamine, 1-(4′-hydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline.     

Two new lignans from twigs of Aglaia odorata

HPLC-guided separation of twigs of Aglaia odorata led to the isolation of eight lignans, including two new ones, 3′-methoxy-N-demethylrocaglamide (1) and 4′-O-demethyl-deacetylaglaxiflorin A (2). Compound 1 showed excellent cytotoxicity against three human cancer cell lines, HeLa, SGC-7901 gastric cancer, and A-549 lung cancer with the values of 0.32, 0.12, and 0.25 μM, respectively.     

CYP3A4 inhibitors isolated from a marine derived fungus <Emphasis Type="Italic">Penicillium</Emphasis> species

More than 50% of clinically used drugs are thought to be metabolized by cytochrome P450 (CYP) 3A4. Discovery of new, inexpensive, CYP3A4 inhibitors will reduce drug dosages needed to cure patients. In our search for new inhibitors of the enzyme CYP3A4, extracts from 102 marine fungi were screened. Seven of the extracts had potent CYP3A4 inhibitory activity. Four aromatic compounds were isolated from an extract of a culture of one of these, a Penicillium sp., and were identified as 3-methoxyphenol (1), 4-methoxyphenylacetic acid (2), 4-(2-hydroxyethyl)phenol (3), and 4-hydroxy-2-methoxyacetanilide (4) by use of spectroscopic data. Interestingly, compound 3 at 250 μg mL⁻¹did not inhibit CYP3A4 whereas compounds 1, 2 and 4 had CYP inhibitory activity with IC₅₀ values of 2.0, 1.6 and 0.41 μg mL⁻¹, respectively.     

Pyrido[3,4-d]pyrimidin-4(3H)-one metabolism mediated by aldehyde oxidase is blocked by C2-substitution

1.?We have previously described C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one derivatives as cell permeable inhibitors of the KDM4 and KDM5 subfamilies of JmjC histone lysine demethylases.

2.?Although exemplar compound 1 exhibited moderate clearance in mouse liver microsomes, it was highly cleared in vivo due to metabolism by aldehyde oxidase (AO). Similar human and mouse AO-mediated metabolism was observed with the pyrido[3,4-d]pyrimidin-4(3H)-one scaffold and other C8-substituted derivatives.

3.?We identified the C2-position as the oxidation site by LC-MS and ¹H-NMR and showed that C2-substituted derivatives are no longer AO substrates.

4.?In addition to the experimental data, these observations are supported by molecular modelling studies in the human AO protein crystal structure.     

(±) Cochlearoids N–P: three pairs of phenolic meroterpenoids from the fungus Ganoderma cochlear and their bioactivities

Three pairs of meroterpenoids (±) cochlearoids N–P (1–3) were isolated from the fruiting bodies of Ganoderma cochlear. Their structures including absolute configurations were assigned by spectroscopic techniques. All the isolated compounds were tested for their inhibitory activities toward BRD4, human cancer cells, and micro-organisms. The results show that the enantiomers of (±)-1 are BRD4 inhibitors, (?)-1 and (+)-3 are cytotoxic against human cancer cells (K562) with IC₅₀ values of 7.68 and 6.68 μM, respectively. Besides compounds (±)-2 and (±)-3 exhibit potent inhibitory activity against Staphylococcus aureus with IC₅₀ values in the range of 5.43–17.99 μM.     

A new chromone and a new aliphatic ester isolated from Daldinia eschscholtzii

Abstract

A new chromone and a new aliphatic ester were isolated from the EtOAc extract of myceliums of Daldinia eschscholtzii. Their structures were elucidated as (R)-5-hydroxy-8-methoxy-2-methylchroman-4-one (1) and (E)-6-(non-3-en-1-yl) -2H-pyran-2-one (2) by interpretation of the spectroscopic evidence.     

Prenylated C6–C3 compounds from the fruits of Illicium simonsii

Two new prenylated C₆–C₃ compounds, 4-epi-illicinone E-12-shikimate (1) and 3-hydroxyillifunone B (2), together with five known prenylated C₆–C₃ compounds (3–7), were isolated from the fruits of Illicium simonsii. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR, CD spectra, and ESI-MS analysis.     

Isolation of 3-O-(4′-Hydroxybenzyl)-β-sitosterol and 4-[4′-(4″-Hydroxybenzyloxy)benzyloxy]benzyl methyl ether from fresh tubers ofGastrodia elata

Two new 4-hydroxybenzyl alcohol derivatives (1 and2) were isolated from the methanol extract obtained from fresh tubers ofGastrodia elata together with 4-hydroxybenzyl methyl ether, 4-hydroxybenzyl alcohol, bis(4-hydroxyphenyl)methane, 4-hydroxybenzaldehyde, β-sitosterol and palmitic acid.1 and2 were identified as 3-O-(4′-hydroxybenzyl)-β-sitosterol and 4-[4′-(4″-hydroxybenzyloxy) benzyloxy)benzyl methyl ether, respectively, according to the spectroscopic data.     

Synthesis and anti-HIV evaluation of the novel 2-(m-chlorobenzyl)-4-substituted-7-methyl-1, 1, 3-trioxo-pyrazolo[4, 5-e] [1, 2, 4]thiadiazines

A novel series of 2-(m-Chlorobenzyl)-4-substituted-1, 1, 3-trioxo-2H,4H-pyrazolo[4, 5-e][1, 2, 4] thiadiazines (7a-k) were synthesized, and evaluated for their anti-HIV replication in MT-4 cell cultures. Compound (7a) showed activity against HIV-1-induced cytopathicity, with an EC₅₀ value of 45.6 μM, but none of the compounds exhibited inhibitory activity against HIV-2.     

Chromone glycosides from Knoxia corymbosa

Four new chromone glycosides, corymbosins K₁-K₄ (3–6), together with two known compounds, noreugenin (1) and undulatoside A (2), were isolated from the whole plant of Knoxia corymbosa (Rubiaceae). The structures of the new compounds were established through extensive NMR or X-ray spectroscopic analysis as 7-O-β-d-allopyranosyl-5-hydroxy-2-methylchromone (corymbosin K₁, 3), 7-O-β-d-6-acetylglucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K₂, 4), 7-O-[6-O-(4-O-trans-caffeoyl-β-d-allopyranosyl)]-β-d-glucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K₃, 5) and 7-O-[6-O-(4-O-trans-feruloyl-β-d-allopyranosyl)]-β-d-glucopyranosyl-5-hydroxy-2- methylchromone (corymbosin K₄, 6). Compounds 2–5 were subjected to test their immunomodulatory activity in vitro.     

Two new triterpenoids from the leaves and stems of Fritillaria hupehensis

Two new cycloartane-type triterpenoids 25-hydroxyl-9,19-cycloart-22-ene-3-one (1) and (23Z)-9,19-cycloart-23-ene-3α,25-diol (2) along with 9,19-cycloart-25-ene-3β, 24ξ-diol (3) and cycloeucalenol (4) have been isolated from the leaves and stems of Fritillaria hupehensis Hsiao et K.C. Hsia. Their structures were elucidated on the basis of spectroscopic analysis.