Labdane and norlabdane diterpenoids from the aerial parts of Leonurus japonicus

A new labdane diterpenoid, leojaponicin (1), a novel norlabdane, methyl 15,16-dinor-7-oxolabda-8-ene-14-oate (2), along with four known labdanes, hispanone (3), leoheteronins A (4) and B (5), 15-methoxyleoheteronin B (6), and three norlabdanes, 14,15,16-trinor-7-oxolabda-8-ene-13-oic acid (7), methyl 14,15,16-trinor-7-oxolabda-8-ene-13-oate (8), 14,15-dinor-8-labdene-7,13-dione (9), and a steroid, stigmast-4-ene-3-one (10), were isolated from a hexane extract of Leonurus japonicus. Their structures were determined using spectroscopic methods, mainly 1-D and 2-D NMR. Compounds 7 and 8 were previously semisynthesized but are reported here for the first time as naturally occurring compounds. In addition, α-glucosidase inhibitory activity of the isolated compounds was evaluated and compound 6 exhibited the strongest effect with IC₅₀ value of 26.7 μM (compared with the positive control acarbose, IC₅₀ = 214.5 μM).     

Voulkensin C–E,new 11-oxocassane-type diterpenoids and a steroid glycoside from Caesalpinia volkensii stem bark and their antiplasmodial activities

A bioassay guided isolation of potential antimalarial molecules from the stem bark of Caesalpinia volkensii Harms (Fabaceae) achieved three new 11-oxocassane-type diterpenoids named voulkensin C (1), D (2) and E (3) together with one steroid glycoside named 3-O-[β-glucopyranosyl(1→2)-O-β-xylopyranosyl]-stigmasterol (4) and seven other known compounds including stigmasterol (5), β-sitosterol (6), oleanolic acid (7), 3-β-acetoxyolean-12-en-28-methyl ester (8), voucap-5-ol (9), caesadekarin C (10), deoxycaesaldekarin C (11). The structures of the new compounds were determined on the basis of extensive spectroscopic data (IR, MS, ¹H and ¹³C NMR and 2D NMR) analyses. The polar extracts revealed moderate to good antiplasmodial activities against chloquine-sensitive (D6) and -resistant strains (W2) of Plasmodium falciparum. Whereas the pure isolates exhibited limited to moderate antiplasmodial activities with compound 4 showing the highest antiplasmodial activities (IC₅₀ values of 4.44 ± 0.88 and 2.74 ± 1.10 μM against D6 and W2 strains, respectively). These results suggest a possible contribution of phytochemicals from C. volkensii stem bark towards inhibition of plasmodial parasites’ growth hence potential antimalarial.     

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.     

Xanthine oxidase inhibitory terpenoids of Amentotaxus formosana protect cisplatin-induced cell death by reducing reactive oxygen species (ROS) in normal human urothelial and bladder cancer cells

The diterpenoids (+)-ferruginol (1), ent-kaur-16-en-15-one (2), ent-8(14),15-sandaracopimaradiene-2α,18-diol (3), 8(14),15-sandaracopimaradiene-2α,18,19-triol (4), and (+)-sugiol (5) and the triterpenoids 3β-methoxycycloartan-24(24¹)-ene (6), 3β,23β-dimethoxycycloartan-24(24¹)-ene (7), 3β,23β-dimethoxy-5α-lanosta-24(24¹)-ene (8), and 23(S)-23-methoxy-24-methylenelanosta-8-en-3-one (9), isolated from Amentotaxus formosana, showed inhibitory effects on xanthine oxidase (XO). Of the compounds tested, compound 5 was a potent inhibitor of XO activity, with an IC₅₀ value of 6.8 ± 0.4 μM, while displaying weak ABTS radical cation scavenging activity. Treatment of the bladder cancer cell line, NTUB1, with 3–10 μM of compound 5 and 10 μM cisplatin, and immortalized normal human urothelial cell line, SV-HUC1, with 0.3–1 μM and 10–50 μM of compound 5 and 10 μM cisplatin, respectively, resulted in increased viability of cells compared with cytotoxicity induced by cisplatin. Treatment of NTUB1 with 20 μM cisplatin and 10 or 30 μM of compound 5 resulted in decreased ROS production compared with ROS production induced by cisplatin. These results indicate that 10 or 30 μM of compound 5 in NTUB1 cells may mediate through the suppression of XO activity and reduction of reactive oxygen species (ROS) induced by compound 5 cotreated with 20 μM cisplatin and protection of subsequent cell death.     

Antiviral anthraquinones from the roots of Knoxia valerianoides

Three new anthraquinones, (2S)-8-carboxy-9-hydroxy-2-(2-hydroxypropan-2-yl)-1,2-dihydroanthra[2,1-b]furan-6,11-dione (1), 1,2,3,6-tetrahydroxy-9,10-anthraquinone (2), and 1,2,3,5,6-pentahydroxy-9,10-anthraquinone (3), as well as four known 9,10-anthraquinones (4–7) and five known triterpenes (8–12), were isolated from the roots of Knoxia valerianoides. Their structures and the absolute configuration of 1 were determined through interpretation of spectroscopic data, including UV, IR, NMR and CD spectra. The isolates were evaluated for their antiviral activities, and compounds 1 and 4 showed inhibitory effects on Coxsackie virus B3 replication with IC₅₀ values of 19.24 μM and 11.11 μM, respectively. Compound 4 showed activity against influenza virus A/Hanfang/359/95 with an IC₅₀ value of 11.11 μM.     

Ehrenasterol and biemnic acid; new bioactive compounds from the Red Sea sponge Biemna ehrenbergi

In continuation of our efforts to identify bioactive compounds from the Red Sea marine sponges, we have recently investigated the organic extract of the sponge Biemna ehrenbergi. This study resulted in the isolation of eight compounds including a new sterol, ehrenasterol (1), a new C₂₄-acetylenic acid, biemnic acid (2), together with six known compounds including a hopanoid, three steroids and two nucleosides. The isolated compounds were identified as (22E)-ergosta-22-ene-8,14-epoxy-3,7-dione (1), (E)-tetracos-8-en-5-ynoic acid (2), (22E)-ergosta-5,8,22-trien-7-one-3β-ol (3), 32,35-anhydrobacteriohopanetetrol (4), (24R)-ergosta-6,22-diene-5,8-epidioxy-3-ol (5), melithasterol B (6), thymidine (7) and 2′-deoxyuridine (8). The structures of the isolated compounds were assigned by different spectral data including 1D and 2D NMR (COSY, HSQC, and HMBC) and high-resolution mass spectrometry. Compound 1 displayed inhibition zone of 20 mm at 100 μg/disc against Escherichia coli in the disc diffusion assay. Similarly, compounds 2 and 4 displayed inhibition zones of 20 and 18 mm respectively against Candida albicans at the same concentration. Compounds 1–3 displayed weak cytotoxic activity against human colon adenocarcinoma (HCT-116) cancer cell line.     

Bioactive chemical constituents from the root bark of Morus australis

Two new pyranoflavonoids, morustralins A (1) and B (2), a new natural benzene derivative, one benzenoid (Z)-1-hydroxy-4-(2-nitroethenyl)benzene (3), and thirty known compounds were isolated and characterized from the root bark of Morus australis. The structures of the new compounds were established from spectroscopic and spectrometric analyses. Ten isolates (1–10) were examined for inhibitory effects on adenosine diphosphate (ADP)-, arachidonic acid (AA)-, and platelet-aggregating factor (PAF)-induced platelet aggregation. Among the tested compounds, compound 3 displayed the most significant inhibition of ADP- and AA-induced platelet aggregation with IC₅₀ values of 9.76 ± 5.54 and 9.81 ± 2.7 μM, respectively. In addition, eight purified compounds (3–10) were examined for inhibition of nitric oxide (NO) production in RAW 264.7 cells and six compounds (3–8) displayed significant inhibitory effects with IC₅₀ values ranging from 2.1 ± 0.3 to 6.3 ± 0.6 μM.     

Incrassamarin A–D: Four new 4-substituted coumarins from Calophyllum incrassatum and their biological activities

Four new 4-substituted coumarins, incrassamarin A (1), B (2), C (3) and D (4) with (7S,8S)-7,8-dihydro-5-hydroxy-7,8-dimethyl-4-propyl-2H,6H-benzo[1,2-b;5,4-b’]dipyran-2,6-dione (5), friedelin, carpachromene, amentoflavone, epiafzelechin and L-quercitrin were isolated from the barks and leaves of Calophyllum incrassatum (Guttiferae). The compounds were isolated and purified by size-exclusion recycling HPLC and column chromatographic techniques. The structures of the compounds were determined by spectroscopic means. The compounds were tested for their cytotoxic activity towards MCF-7 and A-549 cell lines and α-glucosidase enzymatic inhibitory activity. Compound (1) displayed cytotoxic activity against A-549 cell lines with IC₅₀ 87.71 μg/mL and showed inhibition towards α-glucosidase enzymatic activity with IC₅₀ 93.25 μM. This is the first report on the isolation of phytochemicals from the barks and leaves of C. incrassatum and their bioactivities.     

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC₅₀ values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC₅₀ value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC₅₀ values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.     

New cytotoxic protolimonoids from the stem bark of Aglaia argentea (Meliaceae)

Two new protolimonoid compounds, namely, argentinin A (1) and B (2) along with five known triterpenoid compounds, dammar-24-en-3α-ol (3), 3-epi-cabraleahydroxy lactone (4), (E)-25-hydroperoxydammar-23-en-3β,20-diol (5), mixture of eichlerianic acid and shoreic acid (6a and 6b), and dammar-24-en-3α,20-diol (7), were isolated from the stem bark of Aglaia argentea. The structure of new compounds were elucidated by spectroscopic methods including one and two-dimensional NMR as well as high-resolution mass spectrometric analysis. All of the compounds were tested for their cytotoxic effects against P-388 murine leukemia cells in vitro. Among those isolated compounds, argentinin A (1) showed the strongest activity with an IC₅₀ value of 1.27 μg/mL (3.05 μM).     

In vitro and in vivo antimalarial evaluation of semi-synthetic derivatives of gomphostenin

A novel series of semi-synthetic gomphostenin derivatives (1–9) were prepared utilizing C-14 hydroxyl group for the first time and studied for their antimalarial properties. In vitro antiplasmodial activity was evaluated against both the chloroquine sensitive and resistant strains of Plasmodium falciparum. Most of the compounds exhibited superior or comparable antiplasmodial activity compared to parent compound, that is, gomphostenin (GN). Based upon in vitro antiplasmodial activity, compounds with IC₅₀ values less than 10 μM were selected for in vivo antiplasmodial evaluation against Plasmodium berghei infection in mice model. GN derivatives 3 and 5 were found to have curative activity with moderate chemosuppression of 65% and 69%, respectively, at the dose level of 150 mg/kg/day.     

New antimalarials with a triterpenic scaffold from Momordica balsamina

Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of three new cucurbitane-type triterpenoids, balsaminols C–E (1–3). Their structures were elucidated on the basis of spectroscopic methods including 2D NMR experiments (COSY, HMQC, HMBC and NOESY). Balsaminols C–E, together with ten cucurbitacins isolated from the same plant (4–13), were evaluated for their antimalarial activity against the Plasmodium falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2. Most of the compounds displayed antimalarial activity. Compounds 9 and 12 revealed the highest antiplasmodial effects against both strains (IC₅₀ values: 4.6, and 7.4 μM, 3D7, respectively; 4.0, and 8.2 μM, Dd2, respectively). Structure–activity relationships are discussed. Furthermore, the preliminary toxicity toward human cells of compounds 1–5 and 9 was investigated in breast cancer cell line (MCF-7). Compounds were inactive or showed weak toxicity (IC₅₀ values >19.0).     

The regulation of inflammatory cytokine secretion in macrophage cell line by the chemical constituents of Rhus sylvestris

In our preliminary screening study on the anti-inflammatory activity, eight triterpenes, one sterol, and one chalcone were isolated from the CH₂Cl₂-soluble extract of the stems and leaves of Rhus sylvestris Siebold and Zucc (Anacardiaceae). On the basis of their spectroscopic data, these compounds were identified as 10α-cucurbitadienol (1), glut-5-en-3-ol (2), β-amyrin acetate (3), β-amyrin (4) and lupeol (5), cycloart-24-en-3-one (6), cycloart-25-en-3,24-dione (7), 24-hydroxycycloart-25-en-3-one (8), β-sitosterol (9), and 2′-hydroxy-4,4′-dimethoxychalcone (10). All of them were isolated from this plant for the first. Furthermore, the compounds in non-cytotoxic concentrations (0–1.0 μM) were tested for their ability to block inflammatory cytokine secretion in the presence of LPS in the murine RAW264.7 macrophage cell line. Among the compounds that were tested, compounds 8 and 9 reduced the LPS-induced secretion of IL-6, as well as TNF-α, in a mouse RAW264.7 macrophage cell line. Moreover, compounds 2, 3, 7, and 10 specifically diminished only the secretion of TNF-α even in 0.01 μM concentrations. It is thus suggested that they are potential therapeutics of TNF-α-related diseases and conditions, such as transplant rejection, type II diabetes, and atherosclerosis.     

Acetylcholinesterase inhibitory activity and mutagenic effects of Croton penduliflorus leaf extract constituents

Croton penduliflorus is a medicinal plant widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases. The activities demonstrated by leaf extracts indicate that they possess the ability to reduce oxidative damage to cells. Repeated column fractionation of the ethyl acetate fraction of a 20% aqueous methanol leaf extract of C. penduliflorus on Sephadex LH-20 afforded four phenolic compounds: quercetin-3-O-rhamnoside (1), kaempferol-3-O-rhamnoside (2), protocatechualdehyde (3A) and its solvent derived dimer (3B) along with p-hydroxybenzoic acid (4). Compound 3B is described for the first time and its significance in bioassay is briefly outlined. Structure elucidation of the isolated compounds was carried out using spectroscopic techniques. The inhibitory properties of the four compounds against acetylcholinesterase were determined using the microplate assay. The IC₅₀ values of the isolated compounds ranged from 87.9 to 1231.9 μM, with compound 2 having the best inhibitory activity (IC₅₀ = 87.9 μM). The four isolated compounds showed no mutagenic effects against Salmonella typhimurium tester strains TA98 and TA100. The moderate activity demonstrated by these compounds suggests that they could be helpful in the management of neurodegenerative disorders.     

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.     

A new phenylpropanoid and an alkylglycoside from Piper retrofractum leaves with their antioxidant and α-glucosidase inhibitory activity

Two new compounds, piperoside (1) and isoheptanol 2(S)-O-β-d-xylopyranosyl (1→6)-O-β-d-glucopyranoside (11), along with 10 known compounds 3,4-dihydroxyallylbenzene (2), 1,2-di-O-β-d-glucopyranosyl-4-allylbenzene (3), tachioside (4), benzyl-O-β-d-glucopyranoside (5), icariside F₂ (6), dihydrovomifoliol-3′-O-β-d-glucopyranoside (7), isopropyl O-β-d-glucopyranoside (8), isopropyl primeveroside (9), n-butyl O-β-d-glucopyranoside (10), isoheptanol 2(S)-O-β-d-apiofuranosyl-(1→6)-O-β-d-glucopyranoside (12), were isolated from the leaves of Piper retrofractum. Their structures were determined from 1D-NMR, 2D-NMR, and HR-ESI-MS spectral, a modified Mosher’s method, and comparisons with previous reports. All of the isolated compounds showed modest α-glucosidase inhibitory (4.60 ± 1.74% to 11.97 ± 3.30%) and antioxidant activities under the tested conditions.     

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.     

Phenolic compounds from the roots of Ochna schweinfurthiana and their antioxidant and antiplasmodial activities

An investigation of compounds extracted from Ochna schweinfurthiana roots with ethyl acetate led to the isolation of three new compounds 4⿴-methoxylophirone A (1), 4,4⿲,4⿴⿿trimethoxylophirone A (2) and (4E;7Z)-3,8-dicarboxy-1-(O-β-d-glucopyranosyl-(1 ⿿ 6)-O-β-d-glucopyranosyl-2,9-dihydroxyhexeicosa-4,7-diene (3). Six known compounds were also identified, including Calodenone (4), Calodenine B (5), Lophirone A (6), Gerontoisoflavone A(7), 16α,17-dihydroxy-ent-kauran-19-oic acid (8) and 3β-O-d-glucopyranosyl-β-sitosterol (9). This report describes the first time that compounds 4-8 have been isolated from this plant, while 8 has never been identified in the genus Ochna. Some of the isolated compounds were evaluated for their antiplasmodial activity against the chloroquine-sensitive Plasmodium falciparum strain 3D7 and antioxidant activity using DPPH radical scavenging and Ferric reducing-antioxidant power (FRAP) assays. Compound 5 exhibited prominent radical scavenging and FRAP activities, while 7 had weak activity. Compound 1 showed good in vitro anti-plasmodial activity. The structures of the isolated compounds were elucidated by spectroscopic methods and comparisons with prior data in the literature.     

Prenylated C6–C3 compounds from the roots of Illicium henryi

Eleven prenylated C₆–C₃ compounds, illihenryifunones A, B (1, 2), illihenryifunol A (3), illihenryipyranol A (4), illihenryiones A−G (5–11), and three known prenylated C₆–C₃ compounds (12–14), were isolated from the roots of Illicium henryi. Structures of 1–11 were elucidated by spectroscopic methods including NMR, HRESIMS, and CD. The absolute configuration of the 11,12-diol moiety in 5 was determined by observing its induced circular dichroism after addition of Mo₂(OAc)₄ in DMSO. The absolute configuration of C-11 in 4 was determined as S based on the Rh₂(OCOCF₃)₄-induced CD data; the absolute configuration of 3 was determined as R by comparison of its experimental and calculated electronic circular dichroism (ECD). The antioxidant activities of compounds 1–14 were also evaluated. Compound 4 exhibited strong antioxidant activity with an IC₅₀ value of 2.97 ± 1.30 μM, whereas compounds 3 and 8 showed antioxidant activities with IC₅₀ values of 44.36 ± 0.30 and 48.00 ± 2.01 μM, respectively.     

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea

A new lignan, 9′-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4–12) have been isolated from the active fractions, CHCl₃ (IC₅₀, 0.32 μg mL^?1) and EtOAc (IC₅₀, 0.55 μg mL^?1) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC₅₀ values of 3.7 and 3.3 μM, respectively. 9′-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner.