Triterpene tetraglycosides from the sea cucumber Stichopus horrens

Using various chromatographic separations, three triterpene tetraglycosides (1–3), including one new compound, namely stichorrenoside E (1) along with thelenotoside B (2) and deacetyl thelenotoside B (3), were isolated from the MeOH extract of the Vietnamese sea cucumber Stichopus horrens. Their structures were confirmed by spectroscopic experiments, such as 1D and 2D NMR and HR-ESI-MS. Deacetylated thelenotoside B (3) is firstly isolated as a natural product. Among these compounds, thelenotoside B (2) showed strong cytotoxicities against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC₅₀ values from 0.95 ± 0.08 to 1.90 ± 0.13 μM, whereas stichorrenoside E (1) and deacetyl thelenotoside B (3) exhibited significant activities with the IC₅₀ values from 6.87 ± 0.25 to 11.62 ± 1.05 μM.     

New cytotoxic isoprenoid derivatives from the Red Sea soft coral Sarcophyton glaucum

Chemical investigation of the soft coral Sarcophyton glaucum collected from the Red Sea led to isolation of 11 isoprenoidal metabolites (1–11). A new sesquiterpenoid, 6-oxo-germacra-4(15),8,11-triene (1), a new natural cembranoid, sarcophinediol, along with two known sesquiterpenoids (2 and 3) and seven known cembranoids (5–11) was obtained. The structures of the compounds were established based on their NMR, MS, IR and UV spectral data. All compounds were evaluated for their cytotoxicity employing three cancer cell lines (HepG2, MCF-7 and HCT116). Compounds 4 and 6 showed significant cytotoxicity towards HepG2 with IC₅₀ values of 18.8 ± 0.07 and 19.9 ± 0.02 μM; respectively. Compounds 5–7 exhibited potent cytotoxicity against MCF-7 cells with IC₅₀ values of 9.9 ± 0.03, 2.4 ± 0.04 and 3.2 ± 0.02 μM, respectively. Compounds 1, 4 and 5 showed significant activities towards HCT116 cells with IC₅₀ values of 29.4 ± 0.03, 19.4 ± 0.02 and 25.8 ± 0.03 μM, respectively.     

Antiproliferative and cytotoxic secondary metabolites from fruits of Leplaea mayombensis

Two new seco-lanostane-type triterpenes, named mayomlactones A (1) and B (2) were isolated from the fruits of Leplaea mayombensis together with 10 known compounds (3–12). Structures of the new compounds were elucidated by extensive spectroscopic studies. Except compounds 11 and 12, all the other chemical compounds are newly reported from Leplaea genus. From the results of this investigation, compounds 1–10 were examined for antiproliferative activity against HeLa cells as well as cytotoxicity against 3T3 cell line. Compounds 3 and 4 showed moderate antiproliferative activity with IC₅₀ values of 10.4 ± 0.1 and 18.6 ± 0.2 μM, respectively. On the other hand, compounds 1, 4 and 9 showed weak cytotoxicity with IC₅₀ values 44.1 ± 0.5, 55.8 ± 0.7 and 55.1 ± 0.5 μM. Overall, none of the tested compounds showed good selectivity (SI ranging from 0.51 to 3.06) but high toxicity against the 3T3 cell line.     

Three new biflavonoids from the branches and leaves of Cephalotaxus oliveri and their antioxidant activity

Three new biflavonoids, named oliveriflavones A-C (1–3), together with two known flavonoids (quercetin (4) and rutin (5)), were isolated from the endangered plant Cephalotaxus oliveri. The chemical structures of these compounds were elucidated by comprehensive spectroscopic methods including NMR, HRESIMS, IR, UV, and CD spectra. Compounds 1–5 were first isolated from the genus Cephalotaxus. All the compounds were tested for their antioxidant activity. Compounds 4 and 5 showed excellent activity with IC₅₀ values of 0.03 ± 0.06 μM and 0.02 ± 0.10 μM, respectively.     

A new cytotoxic biflavonoid from the rhizome of Wikstroemia indica

One new chalcone-flavone biflavonoid, 3′-hydroxydaphnodorin A (1), together with 12 known biflavonoids (2–13), was isolated from the rhizome of Wikstroemia indica. Their structures were established on the basis of extensive spectroscopic methods. Eight isolated compounds 1–3, 6, 7, 9, 12 and 13 were evaluated for their cytotoxic activities against cancer-derived cell lines Hep3B, HepG2 and CNE2, and 1 was found to possess moderate cytotoxicity against HepG2 and CNE2 cell lines, with IC₅₀ values of 65.5 ± 11.4 and 53.6 ± 10.1 μM, respectively.     

Calaxanthones A-C,three new xanthones from the roots of Calophyllum calaba and the cytotoxicity

Three new xanthones, named calaxanthones A-C (1–3), along with 17 known xanthones (4–20) were isolated from the roots of Calophyllum calaba. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell lines with IC₅₀ values in the range of 0.82–5.04 μM. Furthermore, compound 6 showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC₅₀ values of 7.06, 5.27 and 9.64 μM, respectively. Additionally, compound 7 showed potent cytotoxicity against KB cell with an IC₅₀ value of 4.62 μM.     

Two new polyhydroxylated triterpenoids from Salvia urmiensis and their cytotoxic activity

Two new polyhydroxylated triterpenoids were isolated from the acetone extract of the aerial parts of Salvia urmiensis Bunge. Their structures were elucidated by 1D and 2D NMR and HR-ESI-MS analyses as olean-12-ene-1β,3β,11α,22α-tetraol (1) and urs-12-ene-1β,3β,11β,22α-tetraol (2). The effect of these compounds on cell viability of MCF-7 cells was investigated by the MTT assay. Compounds 1 and 2 showed weak cytotoxicity with IC₅₀ values of 110.23 ± 0.12 and 88.35 ± 0.09 μM, respectively.     

Polar steroid derivatives from the Vietnamese starfish Astropecten polyacanthus

Five polar steroid derivatives, including one new glycosylated polyhydroxysteroid namely polyacanthoside A (1), were isolated from the water-soluble materials from the MeOH extract of the Vietnamese starfish Astropecten polyacanthus using various chromatographic separations. The structure elucidation was confirmed by spectroscopic experiments such as HR-ESI-MS, 1D and 2D NMR. Among the isolated compounds, (20R,24S)-3β,6α,8,15β,24-pentahydroxy-5α-cholestane (3) showed significant cytotoxic effect against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC₅₀ values from 18.03 ± 2.63 to 21.59 ± 3.23 μM.     

Four new phenolic constituents from the rhizomes of Gastrodia elata Blume

Four new gastrodin derivatives containing a trans-cinnamoyl unit (1–4) and nine known compounds (5–13) were isolated from the rhizomes of Gastrodia elata Blume. All these compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine-induced cell death, and compounds 7 and 12 showed potent activities with EC₅₀ values of 10.5 and 10.2 μM, respectively.     

A new phenolic compound with antioxidant activity from the branches and leaves of Pyrus pashia

The branches and leaves of Pyrus pashia are used to cure abdominal pain and diarrhoea in Chinese folk medicine. A new phenilic compound, 4-O-β-d-glucopyranosylbenzyl-benzoate ester (1), along with 21 known ones (2–22) were isolated from the branches and leaves of this plant. Compounds 2 and 3 displayed remarkable antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl radical (IC₅₀ = 13.26 ± 0.04 μM, 13.28 ± 0.11 μM, respectively), which were at the same grade as positive control rutin. The caffeoyl group in compounds 2 and 3 was supposed to play an important role in the antioxidant activities.     

Structure activity relationship of bergenin,p-hydroxybenzoyl bergenin, 11-O-galloylbergenin as potent antioxidant and urease inhibitor isolated from Bergenia ligulata

Ethanol extract of the aerial parts of Bergenia ligulata was subjected to solvent–solvent separation followed by various chromatographic techniques that lead to isolation of bergenine (1), p-hydroxybenzoyl bergenin (2), 11-O-galloylbergenin (3) and methyl gallate (4) as major constituents. Ethyl acetate fraction showed a dose-dependent urease inhibitory pattern with IC₅₀ value of 54μg/mL. Structures of compounds 1 and 3 were established by XRD and 2, 4 by NMR. All these compounds were subjected to DPPH scavenging activity, reducing power assay and urease inhibitory activity. The EC₅₀ 7.45 ± 0.2 μg/mL and 5.39 ± 0.28 μg/mL values in terms of antioxidant and reducing power, respectively, were less for 3. Compounds 1–3 showed moderate to significant urease inhibitory potential with IC₅₀ 57.1 ± 0.7, IC₅₀ 48.4 ± 0.3 and 38.6 ± 1.5. Antioxidant activities and urease inhibitory potential were investigated and compound 3 was found to be the most active.     

Bioactive constituents from Croton sparsiflorus Morong

Whole plant extracts of Croton sparsiflorus in methanol have shown significant enzyme inhibition and antioxidant activities. Bioassay-guided isolation of chloroform fraction at pH 3 resulted in the identification of crotsparinine (1) and crotsparine (2), while sparsiflorine (3) was purified from the chloroform fraction at pH 9. The structures of the compounds were confirmed through spectral analyses (EI-MS, ¹H and ¹³C NMR). The isolated compounds 1–3 exhibited remarkable enzyme inhibition activity with IC₅₀ values 27.01 ± 1.1, 22.26 ± 1.0 and 18.02 ± 1.3 μM in xanthine oxidase and 48.42 ± 1.5, 48.05 ± 1.4 and 7.42 ± 1.0 μM in acetylcholine esterase assays, respectively. These compounds also showed potent radical scavenging and reducing properties in DPPH and FRAP assays, respectively. The present results suggest the validity of the traditional uses of C. sparsiflorus in rheumatism and gout. Furthermore, the isolated noraporphine alkaloids can be useful in the treatment of neurodegenerative diseases.     

Two new polyketides from the fungus Penicillium oxalicum MHZ153

Two new polyketides, penicilloxalones A (1) and B (2), together with 13 known compounds (3–15), were isolated from the ethyl acetate extract of the solid substrate fermentation cultures of the fungus Penicillium oxalicum MHZ153. The structures of the isolates were determined by spectroscopic analysis and comparison of their spectroscopic and physicochemical data with the literature values. Compounds 7 and 11 showed inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC₅₀ values of 0.9 ± 0.2 μM and 87.9 ± 0.7 μM, respectively.     

Isolation of a new cytotoxic polyhydroxysterol from the South China Sea soft coral Sinularia sp.

A new polyhydroxysterol, (22E)-24-methylenecholestane-22-ene-3β,5α,6β-triol (1), together with four known analogues (2–5) were isolated from the South China Sea soft coral Sinularia sp. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. All these compounds exhibited cytotoxic effect against both HepG2 and HeLa cell lines with IC₅₀ values ranging from 8.36 to 37.30 μM. Preliminary structure–activity relationship study identified that the presence of double bonds in the side chains of these polyhydroxysterols significantly reduced the biological effect obtained.     

Neolignan and phenylpropanoid compounds from the fruits of Illicium simonsii Maxim

One new sesqui-neolignan compound, namely, sesqui-illisimonan A (1), one new neolignan, illisimonan A (2), and one new phenylpropanoid compound, illisimoid A (3) were isolated from the fruits of Illicium simonsii Maxim. The structures and absolute configurations of these compounds were determined by extensive spectroscopic, including NMR, circular dichroism and calculated electronic circular dichroism methods. The antioxidant activities of compounds 1–3 were also evaluated. Vitamin E was selected as the positive control (IC₅₀ = 49.73 ± 0.88 μM). Compounds 1 and 2 exhibited in vitro antioxidant activity with an IC₅₀ value of 55.76 ± 1.30 and 59.36 ± 0.50 μM, respectively. However, the compound 3 didn’t show obvious antioxidant activity.     

Cytotoxic oplopane sesquiterpenoids from Arnoglossum atriplicifolium

Pale Indian plantain (Arnoglossum atriplicifolium (L.) H. Rob.) is a plant with traditional medicinal usage among the Cherokee Native American tribe for treating cancer. Two oplopane sesquiterpenoids were isolated from an extract of A. atriplicifolium from Western North Carolina. The compounds were isolated by bioassay-guided fractionation using an MCF-7 breast tumour cell line assay. The known compound (1S,6R,7R,8R)-1-acetoxy-6,7-diangeloxy-8,10-epoxy-2-oxo-oplopa-3,14Z,11,12-dien-13-al (1) had an EC₅₀ value of 9.0 μM against MCF-7 cells, while the new compound (1S,3R,6R,7R,8R,11S)-1-acetoxy-6,7-diangeloxy-8,10,11,13-bisepoxyoplopan-2-one (2) had an EC₅₀ value of 96 μM. The compounds were characterised by 1D and 2D NMR spectroscopy and by comparison with literature values in the case for 1. Based on NOESY analysis, a correction of the relative configuration for 1 is presented. The presence of these compounds may help to explain the folk remedy usage of this plant as an anticancer agent.     

Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol and lupeol isolated from Diospyros lotus L.

In this study, the anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol (1) and lupeol (2), isolated from Diospyros lotus L., were explored. Compound 1 showed a marked concentration-dependent inhibition against 12-O-tetradecanoylphorbol-13-acetate (20 ng/32 pmol)-induced Epstein–Barr virus early antigen activation in Raji cells with IC₅₀ of 270 μg/ml, without significant toxicity (70% viability). Compound 2 showed significant anti-tumour-promoting effect with IC₅₀ of 412 μg/ml, without significant toxicity (60% viability). In heat-induced protein denaturation assay, compound 1 exhibited a concentration-dependent attenuation with a maximum effect of 73.5% at 500 μg/ml with EC₅₀ of 117 μg/ml, while compound 2 exhibited a maximum effect of 59.2% at 500 μg/ml with EC₅₀ of 355 μg/ml. Moreover, in silico docking studies against the phosphoinositide 3-kinase enzyme also show the inhibitory potency of these compounds. In short, both the compounds exhibited a marked anti-tumour-promoting and potent inhibitory effect on thermal-induced protein denaturation.     

New cytotoxic bufadienolides from the roots and rhizomes of Helleborus thibetanus Franch

Abstract

Three new bufadienolides 14β, 16β-dihydroxy-3β-[β-D-glucopyranosyl-(1→6)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (1), 14β-hydroxy-3β-[β-D-glucopyranosyl-(1→4)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (2) and hellebrigenin-3-O-β-D-glucosyl-(1→4)-β-D-glucoside (3), together with eight known bufadienolides (4–11) were isolated from the roots and rhizomes of Helleborus thibetanus. Their structures were elucidated by extensive spectroscopic methods and acid hydrolysis. Compounds 1–7 were evaluated for their cytotoxic activity against HCT116, A549 and HepG2 tumor cell lines. Compound 1 exhibited moderate cytotoxicity against HepG2 cells with IC₅₀ value of 15.1?±?1.72?μM. Compounds 5 and 6 exhibited moderate cytotoxicity against HCT116 cells with IC₅₀ values of 15.12?±?0.58?μM and 13.17?±?2.34?μM, respectively.     

New macrocyclic diterpenes from Euphorbia connata Boiss. with cytotoxic activities on human breast cancer cell lines

Acetone:chloroform (1:2) extract of the aerial parts of Euphorbia connata Boiss. (Euphorbiaceae) was investigated for its diterpenoids. This led to the isolation of one known and two new diterpenes, belonging to the pentahydroxy-13(17)-epoxy-8,10(18)-myrsinadiene and tetrahydroxy-5,6-epoxy-14-oxo-jatropha-11(E)-ene classes. The structures were elucidated based on ¹³C and ¹H NMR as well as 2D NMR, IR and MS spectra and the cytotoxicity for compounds 1–3 were evaluated by using MTT assay against two human breast cancer cell lines. Myrsinane-type compounds – 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (1) and 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (2) – exhibited moderate inhibitory effects, with IC₅₀ values of 24.53 ± 3.39 and 26.67 ± 1.41 μM against the MDA-MB cell line, and 37.73 ± 3.41 and 34.57 ± 2.12 μM against the MCF-7 cell line, respectively. Jatrophane-type diterpene – 5,6-epoxy-8,9,15-triacetyl-3-benzoyl-14-oxo-jatropha-11(E)-ene (3) – showed weak cytotoxicity, with IC₅₀ values of 55.67 ± 7.09 μM against MDA-MB, and moderate cytotoxicity with IC₅₀ values of 24.33 ± 3.21 μM against MCF-7 cell line.     

Neuroprotective effect from stem bark extracts of Knema laurina against H2O2- and Aβ1–42-induced cell death in human SH-SY5Y cells

The stem bark extracts of Knema laurina inhibited the hydrogen peroxide (H₂O₂)- and aggregated amyloid β-peptide 1–42 length (Aβ_1–42)-induced cell death in differentiated SH-SY5Y cells. Exposure of 250 μM H₂O₂ or 20 μM Aβ_1–42 to the cells for 24 h reduced 50% of cell viability. Pretreatment of cells with ethyl acetate extract (EAE) or n-butanol extract (BE) at 300 μg/mL and then exposure to H₂O₂ protected the cells against the neurotoxic effects of H₂O₂. Besides, methanolic extract (ME) at 1 and 10 μg/mL exerted neuroprotective effect on Aβ_1–42-induced toxicity to the cells. These results showed that EAE, BE and ME exhibited neuroprotective activities against H₂O₂- and Aβ_1–42-induced cell death. Flavonoids (3–6) and β-sitosterol glucoside (8) were isolated from the EAE. Compound 1 was isolated from hexane extract, and compounds 2 and 7 were isolated from dichloromethane extract. All these observations provide the possible evidence for contribution in the neuroprotective effects.