Three new prenylated xanthones from Comastoma pedunculatum and their anti-tobacco mosaic virus activity

Comastomaxanthones A–C (1–3), three new xanthones with a rare 2-oxoprenyl substituent, along with three known ones (4–6) were isolated from the aerial parts of Comastoma pedunculatum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. In addition, compounds 1–6 were tested for their anti-tobacco mosaic virus activity. The results showed that all isolated compounds exhibited weak anti-TMV activity with IC₅₀ values ranging from 122.7 to 242.9 μM.     

Three new isobenzofurans from Lavandula angustifolia and their bioactivities

Three new isobenzofurans, lavandulactones A–C (1–3), together with three known ones (4–6), were isolated from the whole herb of Lavandula angustifolia. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New isolates were evaluated for their anti-tobacco mosaic virus (TMV) activities and cytotoxicity activities. The results revealed that compounds 1–3 showed high anti-TMV activity with inhibition rate of 31.8, 29.6 and 33.4%, respectively. These rates are higher than that of positive control. Compounds 1–3 also showed weak inhibitory activities against some tested human tumor cell lines with IC₅₀ values ranging from 1.5 to 5.7 μM.     

Isoflavones from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activities

Three new isoflavones, 4′,8-dihydroxy-6,7-dimethoxyisoflavone (1), 4′,6-dihydroxy-8-methoxycarbonyl-7-methoxyisoflavone (2), 4′,7-dimethoxy-8-hydroxymethyl-6-hydroxyisoflavone (3), together with three known flavones (4–6), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Compounds 1–3 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 1–3 (at the concentration of 20 μM) exhibited anti-TMV activities with inhibition rates of 25.2, 22.6, and 27.4%, respectively.     

Biphenyl derivatives from the twigs of Garcinia bracteata and their biological activities

Three new biphenyl derivatives, bractebiphenyls A–C (1–3), along with five known biphenyl derivatives (4–8) were isolated from the acetone extract of the twigs of Garcinia bracteata. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. The anti-tobacco mosaic virus (anti-TMV) activities of 1–8 were evaluated. Compound 3 showed high anti-TMV activities with inhibition rates of 28.4%, which is close to that of Ningnanmycin (30.2%). Compounds 1–3, 6 and 8 were also tested for their cytotoxicities against five human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7), and 3 showed high cytotoxicities against A549 and PC3 cell with IC₅₀ values of 3.6 and 2.7 μM, respectively.     

Tirucallane triterpenoids from the stem bark of Araliopsis synopsis

Two new tirucallane triterpenoids, 21-methoxy-21,23-epoxy-tirucalla-7,24-dien-3α-ol (1) and 21-methoxy-21,23-epoxy-tirucalla-7,24-diene-1α,3α-diol (2), together with thirteen known compounds were isolated from the CH₂Cl₂ extract of the stem bark of Araliopsis synopsis. The structures of the compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data and comparison with previously known analogs. Compounds 1–10 were tested against bacteria, fungi and plant pathogen oomycetes by the paper disk agar diffusion assay resulting in missing to low activities corresponding with MICs > 1 mg/mL. However, compounds 5–10 exhibited high cytotoxic activity against the human Caucasian prostate adenocarcinoma cell PC-3 line, with IC₅₀ 8.5–12.5 μM compared to the standard Doxorubicin with IC₅₀ = 0.9 μM, while compounds 1, 3 and 4 showed low activity.     

Three new benzophenone glycosides with MAO-A inhibitory activity from Hypericum thasium Griseb.

Purification of n-BuOH fraction from 80% ethanol extract of Hypericum thasium Griseb. resulted in the isolation of three new compounds 3′,4,5′-trihydroxy-6-methoxy-2-O-α-l-arabinosylbenzophenone (1), 3′,4,5′,6-tetrahydroxy-2-O-α-l-arabinosylbenzophenone (2), and 3′,4-dihydroxy-5′-methoxy-2-O-α-l-arabinosyl-6-O-β-d-xylosylbenzophenone (3) along with a known flavonoid glycoside quercetin-3-O-α-l-arabinofuranoside (4). The structures of the new compounds were elucidated by 1D and 2D NMR analysis as well as HRESIMS. The isolated compounds (1–4), as well as quercetin, and kaempferol previously isolated from EtOAc fraction were screened against MAO-A inhibitory activity. When tested against the MAO-A quercetin and kaempferol displayed IC₅₀ values of 19.6, and 17.5 μM, respectively. The IC₅₀ values for MAO-A inhibition by compounds (1–4) were 310.3, 111.2, 726.0, and 534.1 μM, respectively. Standard inhibitor (clorgyline) exhibited MAO-A inhibition with an IC₅₀ value of 0.5 μM.     

Acridone alkaloids from Vepris verdoorniana (Excell & Mendonça) Mziray (Rutaceae)

Two new acridone alkaloids, verdoocridone A (1) and B (4), together with fifteen known compounds were isolated from methanol extracts of the roots and leaves of Vepris verdoorniana. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI- and ESI–MS). The ¹³C NMR values of 1,2,3,5-tetramethoxy-N-methylacridone (2) and 5-methoxyaborinine (3) are also reported. The crude extracts and compounds (1-6) were tested for their antimicrobial activity. The test delivered moderate activities for crude extracts and compounds 1, 5 and 6 against the bacterium Staphylococcus aureus and the fungi Mucor meihei and Candida albicans with MIC values between 115 and 180 μg/mL for extracts and between 21.3 and 29.4 μM for compounds, compared to gentamycin with 0.2 μM and nystatin with 5.2 μM against both fungi. The determination of the radical scanvenging activity using 1,1-dephenyl-2-picrylhydrazyl (DPPH) assay gave moderate antioxidant values for all tested compounds, with IC₅₀ between 0.29 and 0.41 μM, compared to the standard 3-t-butyl-4-hydroxyanisole (BHA) displaying 0.03 μM.     

α-Pyrone derivatives with cytotoxic activities,from the endophytic fungus Phoma sp. YN02-P-3

Four new α-pyrone derivatives phomones C-F (1?4) together with four known compounds (5?8) were isolated from the endophytic fungus Phoma sp. YN02-P-3. Compound 1 is the first example of 6-α,β-unsaturated ester-2-pyrone dimers via intermolecular symmetrical [2 + 2] cycloaddition. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The acetylated product (9) of 1 along with compounds 1–8 were then tested for their cytotoxicity against HL-60, PC-3 and HCT-116 cell lines. Compounds 2, 3, 5 and 9 with acetyl groups showed significant inhibitory activities against the three cell lines with IC₅₀ values in the range 0.52–9.85 μM. while compounds 1, 4 and 6–8 that possess no acetyl group showed no inhibitory activity (IC₅₀ > 50 μM), indicating that the acetyl group at 10- or 12- are essential for their cytotoxic activities. The structure-activity relationships of these phomones were also reported.     

Triterpenoid saponins and C-glycosyl flavones from stem bark of Erythrina abyssinica Lam and their cytotoxic effects.

Six new compounds including two oleanane-type triterpenoid saponins (1, 2) and four C-glycosyl flavones (3–6), along with a known saponin (7), three di-C-glycosyl flavones (8–10) and a glycosyl auronol (11), were isolated from the stem bark of Erythrina abyssinica Lam. The structures of the new compounds, identified as 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucuronopyranosyl]-22-O-β-d-glucopyranosyl sophoradiol (1), 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-β-d-glucuronopyranosyl]-22-O-β-d-glucopyranosyl sophoradiol (2), 6-C-β-glucopyranosyl-8-C-β-quinovopyranosyl apigenin (3), 6-C-β-quinovopyranosyl-8-C-β-glucopyranosyl apigenin (4), 8-C-[6″-O-α-l-rhamnopyranosyl-(1‴ → 6″)]-β-glucopyranosyl 7,4′-dihydroxyflavone (5) and 8-C-[6″-O-β-d-xylopyranosyl-(1‴ → 6″)]-β-glucopyranosyl 7,4′-dihydroxyflavone (6), were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and acid hydrolysis. These new compounds together with the known saponins 7 were evaluated for their cytotoxic activity against MCF-7 (estrogen dependent) and MDA-MB-231 (estrogen independent) cell lines. The new saponin 2 exhibited the highest cytotoxic activity among tested compounds, exerting a selective inhibitory effect against the proliferation of MCF-7 cells, with lower IC₅₀ value (12.90 μM) than that of the positive control, resveratrol (13.91 μM). Structure–activity relationship of these compounds is also discussed.     

Three new arylbenzofurans from Lavandula angustifolia and their bioactivities

Three new arylbenzofurans, 2-(7-methoxy-2-(4-methoxyphenyl)-3-methylbenzofuran-5-yl)ethanol (1), 4-(5-(2-hydroxyethyl)-7-methoxy-3-methylbenzofuran-2-yl)phenol (2), and 2-(6-methoxy-2-(4- methoxyphenyl)-3-methylbenzofuran-5-yl)ethanol (3), together with three known ones (4–6) were isolated from the whole plant of Lavandula angustifolia. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1–3 and 5 were tested for their anti-tobacoo mosaic virus (TMV) activities, and Compounds 1–6 were tested for their cytotoxicity activities. In our assay, Compounds 1–3 showed high anti-TMV activity with inhibition rate of 38.2, 35.2, and 34.0%, which superior to positive control Ningnanmycin. Compounds 1–6 also showed weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 2.2–8.2 μM.     

Chromones from the stems of Cassia fistula and their anti-tobacco mosaic virus activities

Three new chromones, 5-methoxy-2,2-dimethyl-7-(2-oxopropyl)-2,3-dihydrochromen-4-one (1), 5-methoxy-2,2-dimethyl-8-(2-oxopropyl)-2,3-dihydrochromen-4-one (2), and 1-(3,4-dihydro-5-methoxy-2,2-dimethyl-2H-chromen-7-yl)propan-2-one (3), together with four known chromones (4–7) were isolated from the stems of Cassia fistula. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compounds 1–5 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 5 exhibited high anti-TMV activity with inhibition rate of 30.8% at a concentration of 20 μM. The other compounds also exhibited potential anti-TMV activities with inhibition rates in the range of 15.6–22.1% at the same concentration.     

A new megastigmane from Kalanchoe tubiflora (Harvey) Hamet

One new megastigmane, (6S,7R,8R,9S)-6-oxaspiro-7,8-dihydroxymegastigman-4-en-3-one (1) (tubiflorone, 1), and ten known compounds were isolated and characterized from the EtOH extract of Kalanchoe tubiflora (Harvey) Hamet. Structures of these isolates were assigned based on spectroscopic analyses that included 1D and 2D NMR techniques, such as HMQC, HMBC, and NOESY. The anti-inflammatory activities of selected isolated compounds (1–6 and 9–11) were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compounds 1–4, 6, 9, and 11 possessed nitric oxide inhibitory activity with IC₅₀ values ranging from 15.1 ± 0.9 to 98.9 ± 1.3 μM.     

Triterpene compounds isolated from Acer mandshuricum and their anti-inflammatory activity

In our preliminary screening study on the anti-inflammatory activity, a new triterpene compound, aceranol acetate (1), was isolated along with five known compounds: β-amyrin acetate (2); glutinol acetate (3); friedelin (4); glutinol (5); (3β)-d-glucopyranoside-stigmast-5-en-3-yl (6), from the stems and leaves of Acer mandshuricum. The structure of the new triterpene was determined to be 5α,6α-epidioxy-5β,6β-epoxy-9,13-dimethyl-25,26-dinoroleanan-3β-ol acetate by spectroscopic studies. Compounds 2–6 were isolated from this plant for the first. Five triterpene compounds (1–5) showed significant cytotoxic activity with GI₅₀ in the range of 11.1–17.9 μM, whereas steroid compound (6) exhibited moderate activity against four human cancer cell lines (HL-60, SK-OV-3, A549, and HT-29). Furthermore, the anti-inflammatory effects of compounds 1–6 in the non-cytotoxic concentrations (1–100 nM) were evaluated for the inhibitory activity of TNF-α secretion in the lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cell line. Among the compounds tested, compound 2 showed the strongest anti-inflammatory activity with the inhibition rate up to 38.40% at the concentration of 100 nM, whereas other five compounds (2–6) exhibited moderate activity.     

Repenins A–D,four new antioxidative coumarinolignoids from Duranta repens Linn.

Phytochemical investigations on the CHCl₃-soluble fraction of the whole plant of Duranta repens Linn. led to the isolation of four new coumarinolignoids, Repenins A–D (1–4), along with the known coumarinolignoids, cleomiscosin A (5) and durantin A (6). Their structures were determined by modern spectroscopic analysis including 1D and 2D NMR techniques and chemical studies. The compounds (1–6) showed potent antioxidative scavenging activity against DPPH radicals, with IC₅₀ values in the range 0.420–0.625 mM. Repenin B (2) displayed the strongest scavenging potential with IC₅₀ values of (0.420 mM).     

Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity

From the leaves of Nelumbo nucifera (an aquatic plant), one new compound, 24(R)-ethylcholest-6-ene-5α-ol-3-O-β-d-glucopyranoside (1), along with 11 known metabolites (2–12), were isolated and identified by spectroscopic methods including 1D- and 2D NMR. Antifungal activity for (R)-roemerine (3) (IC₅₀/MIC = 4.5/10 μg/mL against Candida albicans) and antimalarial activity for (R)-roemerine (3) and N-methylasimilobine (5) (IC₅₀ = 0.2 and 4.8 μg/mL for the D6 clone, respectively, and 0.4 and 4.8 μg/mL for the W2 clone, respectively) was observed. None of the compounds were cytotoxic to Vero cells up to a concentration of 23.8 μg/mL. NMR data for 10-eicosanol (7) and 7,11,15-trimethyl-2-hexadecanone (10) are presented for the first time. An analysis of the structure–activity relationship shows that the substituents in position C-1 and C-2 of aporphine alkaloids are crucial for the antimalarial activity.     

Antiprotozoal,anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers

Nine dihydroartemisinin acetal dimers (6–14) with diversely functionalized linker units were synthesized and tested for in vitro antiprotozoal, anticancer and antimicrobial activity. Compounds 6, 7 and 11 [IC₅₀: 3.0–6.7 nM (D6) and 4.2–5.9 nM (W2)] were appreciably more active than artemisinin (1) [IC₅₀: 32.9 nM (D6) and 42.5 nM (W2)] against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of the malaria parasite, Plasmodium falciparum. Compounds 10, 13 and 14 displayed enhanced anticancer activity in a number of cell lines compared to the control drug, doxorubicin. The antifungal activity of 7 and 12 against Cryptococcus neoformans (IC₅₀: 0.16 and 0.55 μM, respectively) was also higher compared to the control drug, amphotericin B. The antileishmanial and antibacterial activities were marginal. A number of dihydroartemisinin acetal monomers (15–17) and a trimer (18) were isolated as byproducts from the dimer synthesis and were also tested for biological activity.     

New coumestan and coumaronochromone derivatives from Dalbergia boehmii Taub. (Fabaceae)

Chemical investigation of leaves and heartwood of Dalbergia boehmii resulted in the isolation of two new phenolic compounds, designated dalbergestan (1) and dalbergichromone (2), along with eleven known compounds, carpachromene (3), proanthocyanidin A-2 (4); piceatannol (5); biochanin A (6); macckiain (7); homopterocarpin (8); angolensin (9); medicarpin (10); 2′,7-dihydroxy-4′,5′-dimethoxyisoflavone (11); 2′-methoxyformononetin (12); and genistein (13). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses including, IR, UV, 1D and 2D – NMR as well as HRMS data. Some of the isolated compounds were evaluated for their in vitro insulin secretion activity on isolated mice islets, leishmanicidal activity against L. major (DESTO) promastigotes and in vitro cytotoxicity on MCF-7 cell lines. All tested compounds were inactive on glucose-stimulated insulin secretion at stimulatory glucose (20.0 mM) from MIN6 cells. Compounds 3 (IC₅₀, 70.0 μg/ml), 6 (IC₅₀, 60.3 μg/ml), 7 (IC₅₀, 86.5 μg/ml) and 13 (IC₅₀, 62.6 μg/ml) exhibited low leishmanicidal activity while compound 12 (IC₅₀, 56.8 μg/ml) displayed a moderate activity. Compounds 3 and 5 were found to be active against MCF-7 at 50 μM with IC₅₀ value 33.2 ± 3.79 μg/ml and 42.64 ± 5.05 μg/ml respectively.     

Isolation of antiplasmodial anthraquinones from Kniphofia ensifolia,and synthesis and structure–activity relationships of related compounds

Bioassay-guided separation of the South African plant Kniphofia ensifolia for antiplasmodial activity led to the isolation of two new anthraquinones, named kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone monomers (1, 2 and 5), and four known bisanthraquinones (6–9). The structures of the two new compounds were elucidated based on analyses of their 1D and 2D NMR spectra and mass spectrometric data. The dimeric compounds 6 and 7 displayed the strongest antiplasmodial activity among all the isolated compounds, with IC₅₀ values of 0.4 ± 0.1 and 0.2 ± 0.1 μM, respectively. The two new compounds displayed modest activities, with IC₅₀ values of 26 ± 4 and 9 ± 1 μM, respectively. Due to the synthetic accessibility of the new compounds and the increased activity shown by the dimeric compounds, a structure–activity relationship study was conducted. As a result, one analogue of kniphofione B (4), the caffeic acid derivative of aloe-emodin, was found to have the highest activity among all the aloe-emodin derivatives, with an IC₅₀ value of 1.3 ± 0.2 μM.     

Flavonoids and arylbenzofurans from the rhizomes and roots of Sophora tonkinensis with IL-6 production inhibitory activity

Three new compounds (1–3) and 20 known compounds were isolated from the rhizomes and roots of Sophora tonkinensis, and all the isolates were tested for their inhibitory activity against IL-6 production in HMC-1 cells stimulated by PMA plus ionophore, A23187. Of the tested compounds, compounds 1, 5, 9, and 21 were found to potently inhibit IL-6 production with IC₅₀ values of 1.62, 0.73, 3.01, and 4.02 μM, respectively.     

Phenolic amides from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activities

Three new phenolic amides, tabamides A–C (1–3), together with three known phenolic amides (4–6), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Compounds 1–6 were also tested for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compound 1 exhibited high anti-TMV activity with inhibition rate of 38.6%, which is higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activity with inhibition rates in the range of 15.3–26.5%, respectively.