Novel dammarane saponins from Gynostemma pentaphyllum and their cytotoxic activities against HepG2 cells

Two new dammarane saponins, 2α,3β,12β-trihydroxydammar-20(22),24-diene-3-O-[β-d-glucopyranoxyl(1→2)-β-d-6″-O-acetylglucopyranoside (1, namely damulin C) and 2α,3β,12β-trihydroxydammar-20(21),24-diene-3-O-[β-d-glucopyranoxyl(1→2)-β-d-6″-O-acetylglucopyranoside (2, namely damulin D), were isolated from the ethanol extract of Gynostemma pentaphyllum, which had been heat processed by steaming at 125 °C. The NMR spectroscopic data of the novel saponins were completely assigned by using a combination of 2D NMR experiments including ¹H–¹H COSY, HSQC, and HMBC. Their cytotoxic activities of human liver adenocarcinoma HepG2 cells were evaluated in vitro. They showed cytotoxicities against HepG2 cell line with IC₅₀ of 40 ± 0.7 and 38 ± 0.5 μg/ml, respectively.     

Coumarins from the roots of Prangos uloptera

Three new coumarins, 6-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-prenyletin, 3″-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-oxypeucedanin hydrate and 2″-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-oxypeucedanin hydrate, together with six known coumarins, 3″-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-heraclenol, 3″-O-(β-d-glucopyranosyl)-heraclenol, tortuoside, 3″-O-(β-d-glucopyranosyl)-oxypeucedanin hydrate, heraclenol and oxypeucedanin hydrate, have been isolated from the roots of Prangos uloptera, and the structures of these coumarins were unequivocally determined by spectroscopic means, notably UV, HRESIMS, and 1D and 2D NMR spectroscopy.     

Flavonolacyl glucosides from the aril of Schotia brachypetala Sond. and their antioxidant,antibacterial and antimalarial activities

Two new flavonolacyl glucosides, 3-O-methylquercetin 7-O-[β-D-6″-(E-p-coumaroyl) glucopyranoside] (1) and 3,4′-di-O-methylquercetin 7-O-[β-D-6″-(E-p-coumaroyl) glucopyranoside] (2), four known flavonol glycosides (3–5, 7) and one known dihydroflavonolglucoside (6) were isolated from the aril part of Schotia brachypetala with high-speed countercurrent chromatography (HSCCC) as the primary chromatographic technique. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods and acid hydrolysis. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant, antibacterial and antimalarial activities of selected isolates were evaluated. Strong to moderate antioxidant activity (lowest IC₅₀ of 15.2 μM), moderate to weak antibacterial activity (lowest MIC of 0.13 mg/mL) and moderate antimalarial activity (lowest IC₅₀ of 5.18 μg/mL) compared to the positive controls were observed.     

Dihydrochalcone glucosides and antioxidant activity from the roots of Anneslea fragrans var. lanceolata

Bioassay-guided fractionation of the roots of Anneslea fragrans var. lanceolata led to the isolation of four dihydrochalcone glucosides, davidigenin-2′-O-(6″-O-4″′-hydroxybenzoyl)-β-glucoside (1), davidigenin-2′-O-(2″-O-4″′-hydroxybenzoyl)-β-glucoside (2), davidigenin-2′-O-(3″-O-4″′-hydroxybenzoyl)-β-glucoside (3), and davidigenin-2′-O-(6″-O-syringoyl)-β-glucoside (4), and 13 known compounds. The structures were identified by means of spectroscopic analysis. Davidigenin-2′-O-(6″-O-syringoyl)-β-glucoside (4), 1-O-3,4-dimethoxy-5-hydroxyphenyl-6-O-(3,5-di-O-methylgalloyl)-β-glucopyranoside (5), lyoniresinol (10), and syringic acid (13) showed ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)] cation radical scavenging activity, with SC₅₀ values of 52.6 ± 5.5, 26.0 ± 0.7, 6.0 ± 0.2, and 27.5 ± 0.6 μg/mL in 20 min, respectively. Lyoniresinol (10), isofraxidin (12), and syringic acid (13) also showed DPPH [1,1-diphenyl-2-picrylhydrazyl] radical scavenging activity, with SC₅₀ values of 8.4 ± 1.8, 51.6 ± 2.2, and 4.3 ± 0.7 μg/mL in 30 min, respectively.     

Isolation,characterization and cytotoxic activity of benzophenone glucopyranosides from Mahkota Dewa (Phaleria macrocarpa (Scheff.) Boerl)

Two benzophenone glucopyranosides have been isolated from the nut shell part of Mahkota Dewa. The structures were identified as 2,4′,6-trihydroxy-4-methoxy-benzophenone-2-O-β-d-glucoside (Mahkoside A) and 2,4′,6-trihydroxy-4-methoxy-6″-acetyl-benzophenone-2-O-β-d-glucoside (Mahkoside B). Mahkoside B was recognized as a novel compound. Furthermore, a series of benzophenone glucopyranoside derivatives (compounds 3–18) were synthesized and their bioactivities were characterized. Our results demonstrated that compound 18 has significant cytotoxicity against two esophageal cancer cell lines, stomach cancer cell line and prostate cancer cell line, with IC₅₀ less than 10 μM, indicating its potential activity against cancer cells.     

Two new spirostanol saponins from the the roots and rhizomes of Tupistra chinensis

Two new spirostanol saponins (1) and (2), together with three known saponins (3–5), were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as (20S, 22R)-spirost-25(27)-en-1β, 3β, 4β, 5β-tetraol-5-O-β-d-glucopyranoside (1) and (20S, 22R)-spirost-25(27)-en-1β, 3β, 5β-triol-5-O-β-d-glucopyranoside (2), (20S, 22R)-spirost-25(27)-en-1β, 2β, 3β, 4β, 5β-pentaol-5-O-β-d-glucopyranoside (3), Δ²⁵⁽²⁷⁾-pentrogenin (4) and ranmogenin A (5) on the basis of physicochemical properties and spectral analysis. The isolated compounds were evaluated for their cytotoxic activities against A549 and H1299 tumor cell lines in vitro. Among them, compound 2 showed cytotoxicities against A549 cells (IC₅₀ 52.66 ± 3.12 μmol L⁻¹) and H1299 cells (IC₅₀ 57.29 ± 2.51 μmol L⁻¹), respectively.     

Constituents of Leonotis leonurus flowering tops

Phytochemical investigation of flowering tops of Leonotis leonurus, yielded a new diterpene ester, 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecan-1-yl-palmitate along with five known metabolites. The structures of all compounds were determined by spectroscopic methods including 1D- and 2D NMR spectroscopy. All the isolated compounds were evaluated for antimalarial, cytotoxicity and for antimicrobial activities. Antimalarial activity for luteolin 7-O-β-d-glucopyranoside (4) (IC₅₀ = 2.2 μg/mL for the D6 clone and 1.8 μg/mL for the W2 clone) was observed. Chloroquine and artemisinin were used as positive controls which showed IC₅₀ of 0.016 and 0.0048 μg/mL for the D6 clone, respectively, and IC₅₀ of 0.14 and 0.0047 μg/mL for the W2 clone, respectively. None of the compounds were cytotoxic to Vero cells up to a concentration of 4.76 μg/mL.     

New cytotoxic dihydrochalcone and steroidal saponins from the aerial parts of Sansevieria cylindrica Bojer ex Hook

A new dihydrochalcone, 2‘,4‘-dihydroxy-3‘-methoxy-3,4-methylenedioxy-8-hydroxymethylene dihydrochalcone 1 and two new steroidal saponins, (25S)-ruscogenin-1-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranoside 2, (25S)-ruscogenin-3-O-α-l-rhamnopyranosyl-(1 → 4)-β-d-glucopyranoside 3, together with three known steroidal saponins (25S)-ruscogenin-3-O-β-d-glucopyranoside 4, (25S)-ruscogenin-1-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 3)]-α-l-arabinopyranoside 5 and (25R)-26-O-β-d-glucopyranosyl-furost-5-ene-1β,3β,22α,26-tetrol-1-O-α-L-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 3)]-α-l-arabinopyranoside 6 were isolated from the aerial parts of Sansevieria cylindrica. The structures of the new compounds were established by UV, IR, EI-MS, HR-ESI–MS as well as 1D (¹H,¹³C and DEPT-135) and 2D (HSQC, HMBC and TOCSY) NMR spectral analysis. The isolated compounds 1-6 were assayed for in vitro cytotoxicities against the three human tumor cell lines HT116, MCF7 and HepG2. Compound 1 showed a moderate cytotoxicity against MCF7. Compounds 2, 3 and 6 exhibited moderate cytotoxicities against the three used cell lines and compound 5 showed marked cytotoxicities against all used cell lines.     

Isolation,structural characterization and neuraminidase inhibitory activities of polyphenolic constituents from Flos caryophylli

Neuraminidase (NA) is one of the key surface proteins of the influenza virus, which is an important target for anti-influenza therapy. In the present study, bioassay-guided fractionation led to isolation of two new compounds, rhamnetin-3-O-β-d-glucuronide-6″-methyl ester (1) and rhamnazin-3-O-β-d-glucuronide-6″-methyl ester (2), along with seventeen known compounds (3-19), from the MeOH extract of Flos Caryophylli using in vitro NA inhibition assay. These isolated compounds exhibited significantly inhibitory effects on the NA with IC₅₀ values ranging from 8.4 to 94.1 μM and were found to protect MDCK cells from A (H1N1) influenza infections (EC₅₀ = 1.5–84.7 μM) with very low cytotoxicity to the host cells (CC₅₀ = 374.3–1266.9 μM)), with selective index (SI) ranging from 7 to 297. The primary structure-relationships of these isolates were also discussed.     

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.     

Anti-inflammatory activity of flavonoids from Chrozophora tinctoria

Chemical investigation of Chrozophora tinctoria (L.) A. Juss. growing in Saudi Arabia revealed the isolation of two new acylated flavonoids identified as acacetin-7-O-β-d-[α-l-rhamnosyl(1 → 6)]3″-E-p-coumaroyl glucopyranoside (4) and apigenin-7-O-(6″-Z-p-coumaroyl)-β-d-glucopyranoside (5), in addition to amentoflavone (1), apigenin-7-O-β-d-glucopyranoside (2), apigenin-7-O-6″-E-p-coumaroyl-β-d-glucopyranoside (3) and rutin (6). The structures of isolated compounds were established by 1D, 2D NMR and HRESIMS spectral data, in addition to comparison with literature data. The anti-inflammatory activities of isolated compounds were assessed by measuring the levels of IL-1β, IL-6, TNF-α and PGE₂ in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by phytohaemagglutinin (PHA). At a concentration of 100 μM, compounds 1, 2, 4 and 6 significantly decreased Il-1β, Il-6 and PGE₂ to nearly normal values. All tested compounds caused a dose-dependent decrease in TNF-α level but failed to reach that of the control values.     

Triterpenoid saponins from Sesbania vesicaria

Nine oleanane saponins including three new and six known were isolated from the seeds of Sesbania vesicaria. The new saponins were established as 3-O-[α-l-rhamnopyranosyl-(1 → 3)]-β-d-glucuronopyranosyl-3β,29-dihydroxy-olean-12-en-28-oic acid, 3-O-α-l-rhamnopyranosyl-28-O-β-d-glucopyransoyl-3β-hydroxy-olean-12-en-23-al-28-oate, and 3-O-α-l-rhamnopyranosyl-28-O-β-d-glucopyransoyl-3β,23-dihydroxy-olean-12-en-28-oate. All isolated saponins were assayed for their DNA topoisomerase I inhibition ability and cytotoxicity against A549 human lung adenocarcinoma epithelial cells with no positive activity detected (IC₅₀ > 312 μM and GI₅₀ > 25 μM, respectively).     

New triterpene saponins from Phryna ortegioides

Four new and three known oleanane-type saponins have been isolated from the methanolic extract of Phryna ortegioides, a monotypic and endemic taxon of Caryophyllaceae.The structures of the new compounds were determined as gypsogenic acid 28-O-β-d-glucopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)-O-β-d-glucopyranosyl ester (1), 3-O-α-l-arabinofuranosyl-gypsogenic acid 28-O-β-d-glucopyranosyl-(1→3)-O-[β-d-glucopyranosyl-(1→6)]-O-β-d-glucopyranosyl ester (2), 3-O-α-l-arabinofuranosyl-gypsogenic acid 28-O-β-d-glucopyranosyl-(1→3)-O-[β-d-glucopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)-O-]-β-d-glucopyranosyl ester (3), 3-O-α-l-arabinofuranosyl-16α-hydroxyolean-12-en-23,28-dioic acid-28-O-β-d-glucopyranosyl-(1→3)-O-[β-d-glucopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)]-O-β-d-glucopyranosyl ester (4). Their structures were established by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. Noteworthy, none of isolated compounds possesses as aglycone moiety gypsogenin, considered a marker of Caryophyllaceae family.The cytotoxic activity of the isolated compounds was evaluated against three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma) and DeFew (human B lymphoma) cells. Only compound 6 showed a weak activity against A375 and DeFew cell lines with IC₅₀ values of 77 and 52 μM, respectively. None of the other tested compounds, in a range of concentrations between 12.5 and 100 μM, caused a significant reduction of the cell number.     

New β-carboline and indole alkaloids from Actinomycete Actinomadura sp. BCC 24717

Four new β-carbolines 1–4 and two new indoles 5–6 were isolated together with thirteen known compounds from actinomycete, Actinomadura BCC 24717. Structures of the new compounds, 1–6, were determined by NMR spectroscopic and MS spectrometric analyses. Compound 4 exhibited cytotoxicity to Vero cells and compound 6 showed antifungal activity with IC₅₀ 35.91 μg/mL and 41.97 μg/mL, respectively.     

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.     

Phenolic glycosides from Cucumis melo var. inodorus seeds

A new phenolic glycoside (E)-4-hydroxycinnamyl alcohol 4-O-(2′-O-β-d-apiofuranosyl)(1″ → 2′)-β-d-glucopyranoside (1) was isolated and identified from Cucumis melo seeds together with benzyl O-β-d-glucopyranoside (2), 3,29-O-dibenzoylmultiflor-8-en-3α,7β,29-triol (3) and 3-O-p-amino-benzoyl-29-O-benzoylmultiflor-8-en-3α,7β,29-triol (4). Their structures were elucidated by extensive NMR experiments including ¹H–¹H (COSY, TOCSY, ROESY) and ¹H–¹³C (HSQC and HMBC) spectroscopy and chemical evidence. The multiflorane triterpene esters were identified as new melon constituents.     

Rheediinosides A and B,two antiproliferative and antioxidant triterpene saponins from Entada rheedii

Two triterpenoid saponins have been isolated from the seed kernels of Entada rheedii. Their structures have been established using 1D- and 2D-NMR and mass spectrometry as 3-O-β-d-xylopyranosyl-(1 → 3)-O-α-l-arabinopyranosyl-(1 → 6)-2-acetylamino-2-deoxy-β-d-glucopyranosylentagenic acid 28-O-β-apiofuranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside (Rheediinoside A, 1) and 3-O-β-d-glucopyranosyl-(1 → 3)-O-[β-d-xylopyranosyl-(1 → 3)-α-l-arabinopyranosyl-(1 → 6)]-2-acetylamino-2-deoxy-β-d-glucopyranosylentagenic acid 28-O-β-apiofuranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside (Rheediinoside B, 2). Compounds 1 and 2 were tested for their antiproliferative activity against T98G, A431, PC3 and B16-F1 cell lines, and further for their antioxidant properties. Moderate cytotoxic potency and antioxidant properties were found for these compounds whereas Rheediinoside B was in all assays more active than Rheediinoside A.     

Two new penterpenoid saponins and a new diterpenoid glycoside from Hemsleya chinensis

Two new penterpenoid saponins, hemsloside-Ma4 (1) hemsloside-Ma5 (2), and a new diterpenoid glycoside, hemsloside-Ma6 (3), were isolated from the rhizomes of Hemsleya chinensis. By detailed analysis of the NMR spectra and chemical methods, the structures of new compounds were determined to be 3-O-β-l-arabinopyranosyl-(1 → 3)-O-(6′-methyl ester)-β-d-glucuropyranosyl-oleanolic acid-28-O-β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranoside (1), 3-O-β-l-arabinopyranosyl-(1 → 3)-O-(6′-methyl ester)-β-d-glucuropyranosyl-oleanolic acid-28-O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopy-ranoside (2), and 13ϵ-hydroxylabda-8(17), 14-dien-18-oic acid-18-O-α-l-rhamnopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 4)-O-α-l-rhamnopyranoside (3). Diterpenoid-type compound (3) was isolated from Hemsleya genus for the first time.     

Chemical constituents from the fruit of Gardenia jasminoides and their inhibitory effects on nitric oxide production

Three new iridoid glycosides, 6″-O-trans-caffeoylgenipin gentiobioside (1), genipin 1-O-β-d-apiofuranosyl (1→6)-β-d-glucopyranoside (2), genipin 1-O-α-d-xylopyranosyl (1→6)-β-d-glucopyranoside (3), three new monocyclic monoterpenoids, jasminoside R (4), jasminoside S (5), jasminoside T (6), together with nine known iridoid glycosides (7–15) and three crocetin glycosides (16–18), were isolated from the fruit of Gardenia jasminoides. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Inhibitory effects of the isolated compounds on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated. Compounds 8 and 18 showed strong inhibitory activity on NO production with IC₅₀ values of 11.14 ± 0.67 and 5.99 ± 0.54 μM, respectively.     

New oleanane-type saponins: Leptocarposide B-D,from Ludwigia leptocarpa (Onagraceae)

Three new oleanane-type saponins, leptocarposide B-D (1–3), were isolated from the whole plant of Ludwigia leptocarpa (Nutt.) Hara, together with ten known compounds 4–13.The structures of these compounds were determined by interpretation of their spectral data, mainly HR-TOFESIMS, 1D-NMR (¹H, ¹³C) and 2D-NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY), and by comparison with the literature data. The structures of the new compounds were established as 28-O-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-[α-l-arabinopyranosyl-(1 → 3)]-4-O-(3′-hydroxybutanoyloxy-3-hydroxybutanoyloxy)-β-d-fucopyranosyl zanhic acid (1); 3-O-β-d-glucopyranosyl-28-O-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-4-O-(3′-hydroxybutanoyloxy-3-hydroxybutanoyloxy)-β-d-fucopyranosyl medicagenic acid (2); 3-O-β-d-glucopyranosyl-(1 → 4)-β-d-glucopyranosyl-28-O-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-[α-l- arabinopyranosyl-(1 → 3)]-4-O-(3′-hydroxybutanoyloxy-3-hydroxybutanoyloxy)-β-d-fucopyranosyl zanhic acid (3).