Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells are commonly used as a model for assessing the anti-inflammatory or chemopreventive potential of test compounds. Epimuqubilin A, a norsesterterpene peroxide isolated from marine sponge Latrunculia sp., inhibits nitric oxide production in LPS-stimulated RAW 264.7 cells (IC(50) = 7.6 µM). At both the mRNA and protein levels, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are suppressed in a dose-dependent manner. Mitogen-activated protein kinases (MAPKs), one major upstream signaling pathway involved in the transcription of both COX-2 and iNOS, were not affected by treatment of epimuqubilin A. However, the compound blocked the phosphorylation of inhibitor κB (IκB) kinase (IKKβ), resulting in the stabilization of IκBα, and inhibition of NF-κB p65 nuclear translocation and DNA binding. Levels of phosphorylated IKKα were not affected. This is an unique mechanistic relationship that suggests epimuqubilin A warrants further exploration as a potential therapeutic agent.
A high-throughput phytochemical investigation of Abronia villosa afforded a new rotenoid designated abronione (1) along with the known compounds boeravinone C and lupeol. The structure of 1 was determined using NMR, MS, and optical analysis with < 400 µg of material. Compound 1 displayed moderate cytotoxicity against NCI-H460 and HL-60 human cancer cell lines with IC(50) values of 14 and 36 µM, respectively.
The cytotoxic marine red algal metabolite thyrsiferol (1) was found to inhibit hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D human breast tumor cells (66% inhibition at 3 μM). Compound 1 also suppressed hypoxic induction of HIF-1 target genes (VEGF, GLUT-1) at the mRNA level, and displayed tumor cell line-selective time-dependent inhibition of cell viability/proliferation. Mechanistic studies revealed that 1 selectively suppressed mitochondrial respiration at Complex I (IC(50) 3 μM). Thyrsiferol represents a prototypical, structurally unique electron transport chain inhibitor. The apparent rotenone-like activity may contribute to the observed cytotoxicity of 1 and play an important role in Laurencia chemical defense.
Plant secondary metabolites and their semi-synthetic derivatives continue to play an important role in anticancer drug therapy. In this short review, selected single chemical entity antineoplastic agents from higher plants that are currently in clinical trials as cancer chemotherapy drug candidates are described. These compounds are representative of a wide structural diversity. In addition, the approaches taken toward the discovery of anticancer agents from tropical plants in the laboratory of the authors are summarized. The successful clinical utilization of cancer chemotherapeutic agents from higher plants has been evident for about half a century, and, when considered with the promising pipeline of new plant-derived compounds now in clinical trials, this augurs well for the continuation of drug discovery research efforts to elucidate additional candidate substances of this type.
The ethyl acetate extract of the aerial parts of Ajuga turkestanica afforded 6 neo-clerodane diterpenes, including two novel compounds, 14, 15-dihydroajugachin B (1) and 14-hydro-15-methoxyajugachin B (2), in addition to the known diterpenoids chamaepitin (3), ajugachin B (4), ajugapitin (5) and lupulin A (6). Structures were established through exhaustive NMR spectroscopic analysis and chemical transformation in the case of 1. The full (1)H and (13)C NMR assignment of the C-15 R and S configurations of 14-hydro-15-methoxyajugachin B and chamaepitin were elucidated.
Phytochemical investigation of Hypericum empetrifolium Willd. (Clusiaceae), a species native to Greece and Turkey has led to the bioassay-guided identification of two acylphloroglucinol derivatives with potent in vitro anti-inflammatory activity. Using NMR spectroscopy and mass spectrometry, the acylphloroglucinol derivatives were characterized as 3-geranyl-1-(2'-methylpropanoyl)phloroglucinol (1) and 3-geranyl-1-(2'-methylbutanoyl)phloroglucinol (2). Hypotheses are proposed regarding the biosynthetic origin of these and similar acylphloroglucinols from related Hypericum species. Compounds 1 and 2 were evaluated for in vitro inhibitory activity against COX-1, COX-2 and 5-LOX catalyzed LTB(4) formation. Compound 1 displayed good activity (IC(50) values: 6.0, 29.9, and 2.2 μM, respectively) in all three assays. Compound 2 showed good activity (IC(50) value: 5.8 μM) against LTB(4) formation and moderate activity (IC(50) value: 26.2 μM) against COX-1.
The hexane- and ethyl acetate-soluble extracts of the leaves of Brassaiopsis glomerulata (Blume) Regel (Araliaceae), collected in Indonesia, were found to inhibit aromatase, the rate-limiting enzyme in the production of estrogens from androgens, in both enzyme- and cell-based aromatase inhibition (AI) assays. Bioassay-guided fractionation led to the isolation of six known compounds of the steroid and triterpenoid classes (1-6) from the hexane extract, of which 6β-hydroxystimasta-4-en-3-one (5), was moderately active in the cell-based AI assay. Fractionation of the ethyl acetate extract afforded seven pure isolates (7-13) of the modified peptide, fatty acid, monoterpenoid, and benzenoid types, including six known compounds and the new natural product, N-benzoyl-L-phenylalanine methyl ester (9). The absolute stereochemistry of 9 and the other two peptides, 7 and 8, was determined by Marfey's analysis. Linoleic acid (10) was found to be active in the enzyme-based AI assay, while 9 and (-)-dehydrololiolide (12) showed activity in the cell-based AI assay.
A new tripeptide, pre-sclerotiotide F (3), was isolated from a marine sediment-derived fungus, Aspergillus insulicola, along with five known compounds, one of which was new at the time of isolation, scerotiotide F (4). The absolute configuration elucidation of the new compound was determined using a combination of NMR, HR-ESI-MS, and optical rotation analyses. Cytotoxicities were measured in vitro against selected cancer cells. The effects of pre-sclerotiotide F (3) and sclerotiotide F (4) on LPS-induced NF-κB and iNOS expression were also measured.
A chlorinated withanolide, 6α-chloro-5β,17α-dihydroxywithaferin A (1), and nine known withanolides, 6α-chloro-5β-hydroxywithaferin A (2), (22R)-5β-formyl-6β,27-dihydroxy-1-oxo-4-norwith-24-enolide, withaferin A, 2,3-dihydrowithaferin A, 3-methoxy-2,3-dihydrowithaferin A, 2,3-didehydrosomnifericin, withanone, withanoside IV and withanoside X, were isolated from Withania somnifera (Solanaceae). All structures were elucidated on the basis of spectroscopic methods (IR, HRESIMS, 1D/2D NMR). X-ray crystallography confirmed the absolute configuration of 1.
Scientists engaged in the research of natural products often either conduct field collections themselves or collaborate with partners who do, such as botanists, mycologists, or SCUBA divers. The information gleaned from such collecting trips (e.g. longitude/latitude coordinates, geography, elevation, and a multitude of other field observations) have provided valuable data to the scientific community (e.g., biodiversity), even if it is tangential to the direct aims of the natural products research, which are often focused on drug discovery and/or chemical ecology. Geographic Information Systems (GIS) have been used to display, manage, and analyze geographic data, including collection sites for natural products. However, to the uninitiated, these tools are often beyond the financial and/or computational means of the natural product scientist. With new, free, and easy-to-use geospatial visualization tools, such as Google Earth, mapping and geographic imaging of sampling data are now within the reach of natural products scientists. The goals of the present study were to develop simple tools that are tailored for the natural products setting, thereby presenting a means to map such information, particularly via open source software like Google Earth.
Two new acylated flavonol pentaglycosides were isolated from the butanolic extract of Baphia nitida leaves by Sephadex LH-20 and preparative HPLC. Structural elucidation of kaempferol 3-O-β-d-xylopyranosyl(1→3)-(4-O-E-p-coumaroyl-α-l-rhamnopyranosyl(1→2))[β-d-glucopyranosyl(1→6)]-β-d-galactopyranoside-7-O-α-l-rhamnopyranoside (1) and kaempferol 3-O-β-d-xylopyranosyl(1→3)-(4-O-Z-p-coumaroyl-α-l-rhamnopyranosyl(1→2))[β-d-glucopyranosyl(1→6)]-β-d-galactopyranoside-7-O-α-l-rhamnopyranoside (2) was achieved using UV, NMR, and mass spectrometry, indicating the presence of trans or cis isomers of p-coumaric acid moiety in these novel structures. The antioxidant activity of the two compounds was assessed in the peroxynitrite assay.
A phytochemical investigation of the aerial parts of Brassica rapa L. ‘hidabeni’, turnip resulted in the isolation of three new chalcone glycosides, 4′-O-β-d-glucopyranosyl-4-hydroxy-3′-methoxychalcone (1), 4′-O-β-d-glucopyranosyl-3′,4-dimethoxychalcone (2) and 4,4′-di-O-β-d-glucopyranosyl-3′-methoxychalcone (3) along with three known glycosides. The structures of the three newly isolated chalcone glycosides were elucidated on the basis of 1D and 2D NMR and mass spectroscopy.
The volatile emissions of various plant parts of almonds have been studied via various techniques in the past. These analyses have typically been performed on single cultivars and hence may not be representative of the volatiles found in an entire almond orchard. Recent reports suggest some almond volatiles exhibit semiochemical activities for the navel orangeworm (NOW), a major insect pest of almonds; thus, the volatile composition of the comprehensive almond orchard would be helpful to research concerning NOW. The ambient volatile emissions of an almond orchard containing the cultivar Nonpareil and associated pollenizers were collected at four intervals during the 2009 growing season from orchards in the south Central Valley of California. The volatiles hexanal, octanal, nonanal, benzaldehyde, acetophenone, ethyl benzoate, methyl salicylate, and phenol were consistent in their presence and in relatively high amounts. The orchard volatile composition was analyzed via electroantennogram (EAG) analysis, which produced strong responses from NOW antennae.Graphical abstractAmbient almond orchard volatiles representative of the semiochemical medium insects may encounter during flight were collected periodically during the 2009 growing season. The orchard emissions were acquired using a large-scale ambient volatile collection system.Highlights► Ambient volatiles were collected from a commercial almond orchard. ► The collected volatiles were representative of the bouquet an insect may encounter. ► The collected volatiles provide relative trends of volatile emissions. ► Samples of the bouquets elicited relatively large EAG responses.
We prepared soy isoflavonoids related to equol, a potent estrogenic compound metabolized from daidzein. These products were subjected to a competitive enzyme-linked immunosorbent assay to obtain highly selective anti-equol monoclonal antibody.
The n-butanol fraction (BF) of bark of Pecan tree, Carya illinoinensis (Wangenh) K. Koch (Juglandaceae) afforded two new flavonol methyl ether: caryatin-3′ sulfate (6) and caryatin-3′ methyl ether-7-O-β-d-glucoside (7) while five known phenolics (1–5) were isolated from its ethyl acetate fraction (EAF). The structures of isolated compounds were established based on 1D and 2D NMR spectroscopy. The isolated compounds were investigated for their hypoglycaemic, antioxidant as well as the aldose reductase (AR) inhibitory effect in lenses of streptozocin diabetic rats. All the isolated compounds showed significant hypoglycaemic and antioxidant activities, except 5 and 6. A marked AR-inhibitory effect was identified for compounds 2, 3 and 7.Graphical abstractTwo new flavonol methyl ether: caryatin-3′ sulfate (6) and caryatin-3′ methyl ether-7-O-β-D-glucoside (7) were isolated from Carya illinoinensis bark together with five known metabolites. The isolated compounds were investigated for their hypoglycaemic, antioxidant as well as the aldose reductase (AR) inhibitory effect in lenses of streptozotocin diabetic rats.Highlights► Seven phenolic compounds were characterized from bark of Pecan tree; two of them are new and the others are known. ► Hypoglycemic, antioxidant and aldose reductase inhibitory effect in lenses of diabetic rats were evaluated for the compounds. ► Compound 3 and its glucoside 7 revealed the highest hypoglycaemic and AR-inhibitory effects.
Three new neo-clerodane diterpenoids, named scutelinquanines A–C (1–3), were isolated from the whole plant of Scutellaria barbata. Their structures were established on the basis of detailed spectroscopic analyses. In vitro, the isolated three new compounds showed significant cytotoxic activities against three human cancer lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC50 values in the range 2.7–6.7μM.
A phytochemical investigation of the leaves of Vitex quinata (Lour.) F.N. Williams (Verbenaceae), guided by a cytotoxicity assay against the MCF-7 human breast cancer cell line, led to the isolation of a new δ-truxinate derivative (1) and a new phytonoic acid derivative (2), together with 12 known compounds. The structures of the new compounds were determined by spectroscopic methods as dimethyl 3,4,3′,4′-tetrahydroxy-δ-truxinate (1) and methyl 10R-methoxy-12-oxo-9(13),16E-phytodienoate (2), respectively. In a cytotoxicity assay, (S)-5-hydroxy-7,4′-dimethoxyflavanone (3) was found to be the sole active principle, with ED50 values of 1.1–6.7 μM, respectively, when tested against a panel of three human cancer cells. Methyl 3,4,5-O-tricaffeoyl quinate (4) showed activity in an enzyme-based ELISA NF-κB p65 assay, with an ED50 value of 10.3 μM.Graphical abstractA phytochemical investigation of the leaves of Vitex quinata (Lour.) Williams, guided by a cytotoxicity assay against the MCF-7 human breast cancer cell line, led to the isolation of a new δ-truxinate derivative (1) and a new phytonoic acid derivative (2), together with 12 known compounds. In a cytotoxicity assay, (S)-5-hydroxy-7,4′-dimethoxyflavanone (3) was found to be the sole active principle, with ED50 values of 1.1–6.7 μM, respectively, when tested against a panel of three human cancer cells. Methyl 3,4,5-O-tricaffeoyl quinate (4) showed activity in an enzyme-based ELISA NF-κB p65 assay, with an ED50 value of 10.3 μM.Highlights► A new δ-truxinate derivative and a new phytonoic derivative, together with 12 known compounds were isolated from the leaves of Vitex quinata. ► The isolate (S)-5-hydroxy-7,4′-dimethoxyflavanone was found to be active against a panel of three human cancer cells in cytotoxicity assays. ► Methyl 3,4,5-O-tricaffeoyl quinate showed activity in an enzyme-based ELISA NF-κB p65 assay.
Two novel biologically active short peptides, aeruginosins KY642, KY608 and the known aeruginosin 98A were isolated from the cyanobacterium Microcystis sp. strain (IL-323), which was collected from a water reservoir near Kfar-Yehoshua, Valley of Armageddon, Israel. Aeruginosins KY642, KY608 and 98A are linear modified peptides containing four building blocks, one of which is the modified amino acid, Choi (2-carboxy-6-hydroxyoctahydroindole). Aeruginosin KY642 and aeruginosin KY608 inhibit the activity of the photolytic enzyme trypsin with IC50 of 1.4 and 1.7 μg/mL, respectively.Graphical abstractTwo novel biologically active short peptides, aeruginosins KY642, KY608 and the known aeruginosin 98A were isolated from the cyanobacterium Microcystis sp. strain (IL-323).
Two new carabrane sesquiterpenes, 4,8-dioxo-6β-methoxy-7β,11-epoxy carabrane (1), and its isomer, 4,8-dioxo-6β-methoxy-7α,11-epoxy carabrane (2) were isolated from the roots of Vladimiria souliei. Their structures were elucidated by spectroscopic methods (IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR).
Two new diterpenes, including one with an unprecedented 6/6/8 carbon ring skeleton (curcuminol D, 1) and another with 19 carbons (curcuminol E, 2), were isolated from the radix of Curcuma wenyujin. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. Compounds 1 and 2 were tested in vitro for their cytotoxic activity against the human cancer cell lines HL-60 and K562. Compound 1 exhibited medium cytotoxicity with IC50 values of 11.2 and 3.2 μg/mL, respectively, and compound 2 showed better activity against the above cancer cell lines with IC50 values of 4.2 and 2.7 μg/mL, respectively.Graphical abstractTwo new unusual diterpenes, curcuminols D and E (1 and 2) were isolated from the Radix of Curcuma wenyujin. Compounds 1 and 2 presented medium cytotoxic activity against the HL-60 and K562 cancer cell lines.
The naphthoquinones, lapachol (1), plumbagin (2), 2-isopropenyl-9-methoxy-1,8-di-oxa-dicyclopenta[b,g]naphthalene-4,10-dione (3), 9-hydroxy-2-isopropenyl-1,8-dioxa-dicyclopenta[b,g]naphthalene-4,10-dione (4), 2-(1-hydroxy-1-methyl-ethyl)-9-methoxy-1,8-dioxa-dicyclopenta[b,g]naphthalene-4,10-dione (5) and 5,7-dihydroxy-8-methoxy-2-methyl-1,4-naphthoquinone (6) were isolated isolated from roots of Plumbago zeylanica. The new constituents (3–5) in addition to known compounds (1, 2 and 6) were characterized by spectral analysis (UV, IR, 1D & 2D NMR and MS).
Hoodia gordonii, with the perceived active ingredient P57 (a steroidal glycoside), is a succulent plant which has gained commercial popularity as an anti-obesity preparation. The content of P57 is used as an indication of the quality of the raw material. Traditionally, quantification of P57 is performed using liquid-chromatography coupled to mass spectrometry (LC–MS) which is expensive and laborious. Vibrational spectroscopy methods such as FT-Raman spectroscopy offer a simple, less expensive and rapid alternative. The potential of FT-Raman to quantify and identify the location of P57 in H. gordonii raw plant material was investigated. LC–MS was used to determine the concentration of P57 in 145 plant samples and the data was used to develop a calibration model with chemometric techniques based on the partial least squares projections to latent structures (PLS) algorithm. The performance of the calibration model was evaluated according to the root mean square error of prediction (RMSEP) and correlation coefficient (R2). Pre-processing with orthogonal signal correction (OSC) yielded a model which predicted P57 content based on the FT-Raman spectra with a correlation coefficient (R2) value of 0.9986 and an RMSEP of 0.004%. These results demonstrate that FT-Raman spectroscopy holds great potential to rapidly quantify P57 in H. gordonii raw material with high accuracy as an alternative to LC–MS analysis. In addition, the spatial distribution of P57 in a cross-section of an H. gordonii stem sample was demonstrated using FT-Raman mapping showing that P57 is concentrated throughout the cortex which was confirmed with LC–MS.
As part of an on-going project to isolate antibacterial compounds from rare conifer species, a new abietane diterpene, 2β-acetoxyferruginol was isolated from the stem bark of Prumnopitys andina. Molecular modelling studies were conducted to explain some of the NOEs observed in the A-ring of this compound and to support assignment of relative stereochemistry. This new compound had antibacterial activity at 8 μg/ml against two effluxing strains of Staphylococcus aureus, but interestingly was inactive at 128 μg/ml against a wild-type strain and against a methicillin-resistant (MRSA) clinical isolate. We have previously demonstrated that ferruginol is active against these four S. aureus stains and therefore the results indicate that the presence of the acetoxy group has a detrimental effect on antibacterial activity against certain strains. 2β-Acetoxyferruginol was also assayed against Propionibacterium acnes and was active at 4 μg/ml.Graphical abstractA new antibacterial abietane diterpene, 2β-acetoxyferruginol (1) was isolated from the stem bark of Prumnopitys andina and its structure was determined by spectral means. Activity was assessed against multidrug and methicillin-resistant Staphylococcus aureus (MRSA) strains and with Propionibacterium acnes, the major bacterial cause of acne, and the minimum inhibitory concentration value against P. acnes was 4 μg/ml.
In the differentiation of a 3T3-L1 preadipocyte to a mature adipocyte, intensive triglyceride (TG) synthesis and intracellular accumulation of lipid droplets are induced. Lupeol, a lupane triterpene, markedly blocked TG synthesis and the accumulation of lipid droplets in 3T3-L1 cells stimulated with differentiation inducers. The analysis of gene expressions by quantitative real-time RT-PCR demonstrated that lupeol markedly inhibited adipogenic transcription factors, adipogenic enzymes, and adipocytokines in mature 3T3-L1 cells. These findings suggested that lupeol strongly inhibited 3T3-L1 cell differentiation into mature adipocytes in vitro.Graphical abstractLupeol, a lupane triterpene, blocks the accumulation of lipid droplets, a cell differentiation marker of 3T3-L1 preadipocytes. The analysis of gene expressions revealed that lupeol inhibited triglyceride synthesis in mature 3T3-L1 cells by attenuating adipogenic enzymes.
Five new dihydronaphthalenones (1, 2a/2b, 3a/3b), four of which were isolated as two inseparable mixtures of isomers, together with two known compounds, 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (4) and siderin (5), were identified as secondary metabolites of the endophytic fungus Botryosphaeria sp. BCC 8200. The structures were elucidated by interpretation of NMR spectroscopic and mass spectrometry data. Compounds 2a/2b, 3a/3b, and 5 exhibited weak cytotoxic activities against cancer cell lines.
The investigation of the ethanol extract of Acanthospermum australe, collected in the province of Misiones, Argentina, yielded eight melampolides (1–8) of the acanthospermal type. Two of them, 8β-hydroxy-9α-(2-methylbutyryloxy)-14-oxo-acanthospermolide (3) and 9α-hydroxy-8β-(2-methylbutyryloxy)-14-oxo-acanthospermolide (7) are new compounds. Two other compounds (4 and 8) have been previously reported, and the NMR data of 4 are corrected. Compounds 1, 2, 5 and 6 have not been previously reported, but are probably artifacts formed during extraction. Compounds 3, 6 and 7 showed slight antibiotic activity against Gram-positive bacteria.
A new sesquiterpene was isolated from extracts of Sumatra benzoin gum. Its structure was elucidated by means of mass spectrometry and two-dimensional NMR. This new compound presented an acenaphthylene-type skeleton unpreviously described among the family of sesquiterpene hydrocarbons.
d, l-Tryptophan as the precursor of melatonin and Achillea millefolium L. as the plant cell tissue were used in order to force the plant enzymatic system to enhance the production of melatonin.The biotransformation protocol was performed by adding the precursor to the freshly chopped plant material suspended in water and stirred at room temperature in total darkness. The melatonin content was evaluated by LC-DAD-ESI-MS. The precursor-treated sample gave at least six times (345 ng/gfresh plant) the melatonin amount usually produced in young plants of A. millefolium L. (50 ng/gfresh plant).The present study shows that, in principle, adding a specific precursor to a suitable freshly chopped plant material can significantly enhance a secondary metabolite production.Graphical abstractd, l-Tryptophan as the precursor and Achillea millefolium L. as the plant cell tissue were used in order to enhance the production of melatonin in the freshly chopped plant material. After extraction, the melatonin content was evaluated by LC-DAD-ESI-MS. The yield of melatonin was at least six times the amount generally produced in the cultivated A. millefolium L. young plants.
An investigation into the keto-enol relationships in a number of hop acids has been undertaken. These provided samples to enable X-ray analyses of both natural 1 and unnatural humulone 5 to be carried out. Our results suggest that the configuration of humulone 1 may have been incorrectly assigned. An in vitro investigation into the biological activity of hop acids suggests that both humulone 1 and lupulone 2 exhibit significant activity against some human cancer cells. Our results provide evidence to show that they inhibit cell growth, induce caspase dependent apoptosis and inhibit adhesion of some cancer cells to bone tissue.
Salvianolic acids (SAs) extracted from Salvia miltiorrhiza could inhibit ADP-induced aggregation of rat washed platelets. To elucidate the cellular mechanism of the inhibitive effect on platelet aggregation, a proteomic method was used to find the possible target-related proteins of SA in platelets. Treatment of 150 μg/ml SA caused the regulation of platelet levels of 12 proteins, which play important roles in calcium homeostasis, antioxidant system and cytoskeleton structure. The proteomic result was also confirmed by Western blotting.Graphical abstractWe report the result of identifying the possible target-related proteins of salvianolic acids (SAs) in rat platelets. Twelve proteins that might be related to the inhibitive effect of salvianolic acids on platelet aggregation were identified.
Phytochemical studies on the methanolic extract of Drypetes gossweileri afforded N-β-d-glucopyranosyl-p-hydroxyphenylacetamide (1), p-hydroxyphenylacetic acid (2), p-hydroxyphenyl-acetonitrile (3), p-hydroxyacetophenone (4), 3,4,5-trimethoxyphenol (5), dolichandroside A (6), and β-amyrone (7). Compounds 1–7 were identified with the aid of extensive NMR and MS spectroscopic studies. Compound 1 was a new natural product and was isolated for the first time from plant containing N-glucose moiety incorporated in its structure. Compounds 1–7 exhibited moderate to the weak source anti-α-glucosidase inhibitory activity. Compound 7 exhibited moderate anti-acetylcholinesterase (AChE) activity while the rest of the isolates were weakly active in this bioassay. Compounds 1–7 also showed moderate anti-fungal activity.Graphical abstractFrom the methanolic extract of Drypetes gossweileri, one new natural product, N-β-d-glucopyranosyl-p-hydroxyphenylacetamide (1), along with six known natural products, p-hydroxyphenylacetic acid (2), p-hydroxyphenylacetonitrile (3), p-hydroxyacetophenone (4), 3,4,5-trimethoxyphenol (5), dolichandroside A (6), and β-amyrone (7) were isolated. All of the isolates exhibited different levels of anti-α-glucosidase, anti-acetylcholinesterase and anti-fungal activities.Research highlightsChemical investigation of Drypetes gossweileri afforded one new natural product, N-β-d-glucopyranosyl-p-hydroxyphenylacetamide (1), along with six known natural products. All of the isolates exhibited different levels of anti-α-glucosidase, anti-acetylcholinesterase and anti-fungal activities.
A new triterpenoid, 2α, 3β, 20β, 23-tetrahydroxy-urs-12, 19 (29)-dien-28-oic acid, together with eight known triterpenoids, was isolated from the aerial parts of Salvia chinensis. Their structures were identified by spectroscopic analyses. The antiproliferative effects and differentiation induction abilities of these compounds were determined in human leukemia HL-60 cells.Graphical abstractA new triterpenoid, 2α, 3β, 20β, 23-tetrahydroxy-urs-12, 19 (29)-dien-28-oic acid, together with eight known triterpenoids, was isolated from the aerial parts of Salvia chinensis. The antiproliferative and differentiation induction abilities of these compounds were determined in human leukemia HL-60 cells.
In vitro hydroxylation of the norlignan agatharesinol to sequirin C and metasequirin C was demonstrated for the first time. After incubating agatharesinol with a microsomal preparation from the heartwood side of the intermediate wood of Cryptomeria japonica in the presence of cofactors, the aromatic ring-monohydroxylated derivatives of agatharesinol, sequirin C and metasequirin C, were formed. Although hydroxylation hardly occurred in the absence of cofactors, it could be initiated by adding NADPH or NADH, and was enhanced by further adding FAD or FMN. When microsomal preparations from the sapwood or from the sapwood side of the intermediate wood were used, hydroxylation did not occur. This in vitro conversion of the norlignans indicates that the hydroxylation of agatharesinol to sequirin C and metasequirin C is part of the in vivo biosynthetic pathway of norlignans. Another C. japonica norlignan, sugiresinol, which is a side chain-cyclized isomer of agatharesinol, does not seem to be accepted as a substrate, because hardly any hydroxysugireinol was formed after similar incubation with the enzyme.
The phytochemical investigation of the methylene chloride/methanol extract of the aerial parts of Artemisia herba-alba afforded two new natural sesquiterpene lactones 1β,9β-diacetoxyeudesm-3-en-5α,6β,11βH-12,6-olide (1) and 1β,9β-diacetoxyeudesm-4-en-6β,11βH-12,6-olide (2). The structures of the compounds were determined by comprehensive NMR studies, including DEPT, COSY, NOESY, HMQC, HMBC and HRMS.Graphical abstractPhytochemical investigation of the methylene chloride/methanol extract of the aerial parts of Artemisia herba-alba afforded two new natural sesquiterpene lactones. The structures of the compounds were determined by comprehensive NMR studies, including DEPT, COSY, NOESY, HMQC, HMBC and HRMS.
Analysis of the secondary metabolites content of the brown alga Dictyota ciliolata, collected from Oualidia lagoon (Morocco), revealed the presence of xenicane and guaiane homologous diterpenes. Two new xenicanes, 1 and 2, co-occurring with the known dictyodial, dictyol C and dictyol H, have been isolated and characterized by spectral methods, mainly by NMR techniques. Compound 2 displayed mild antifungal activity against Candida albicans.
The alkaloids of Sceletium tortuosum (Mesembryanthemaceae) exhibit important pharmacological properties and are used for the treatment of psychiatric and psychological conditions, including depression, anxiety, drug dependence, bulimia and obsessive-compulsive disorder. The all-liquid technique of high-speed countercurrent chromatography provides an excellent tool for the rapid isolation of these alkaloids in high yields.Graphical abstractMesembrine (1) and other pharmacologically active alkaloids from Sceletium tortuosum (Mesembryanthemaceae) were isolated by high-speed countercurrent chromatography. This was a more efficient method than chromatography on solid phase supports.Highlights► Sceletium alkaloids have important pharmacological properties. ► The alkaloids were separated by high-speed countercurrent chromatography. ► Better yields were obtained than by conventional chromatographic methods.
Three new endiandric acid derivatives, beilschmiedic acids D, E and beilschmiedin were isolated from the stem bark of Beilschmiedia anacardioides together with the known compounds bisabolene and tricosanoic acid. Their structures were determined on the basis of spectroscopic analysis.
Several species belonging to the genus Rhamnus (Rhamnaceae), comprising ones among which are found the most typical plants of the Italian flora, are known to contain biologically active anthraquinone secondary metabolites. Although several Rhamnus species were so far investigated, no information is available concerning the content and relative abundances of anthraquinones in R. saxatilis. In this study we used a simple, reliable, and accurate analytical method to determine the anthraquinones in bark of R. saxatilis. This allowed us also to trace a comparative study on the efficacy of different extraction solvents in ultrasonication time dependent assays. Separation and quantification of anthraquinones were accomplished using a C18 column with the mobile phase of H2O:methanol (40:60, v/v, 1% formic acid) at a flow rate of 0.7mL/min and a detection wavelength of 254nm, while the qualitative analyses were also achieved at a wavelength of 435nm.Finally, the described HPLC method, was used to obtain a specific chemical fingerprint for this species in comparison with other species from the same family.
A new oleanane-type triterpene saponin, β-d-glucopyranosyl 2α,3β,6β-trihydroxy-23-galloylolean-12-en-28-oate (1), together with four known oleanane-type pentacyclic triterpenoids, combregenin (2), arjungenin (3), arjunglucoside I (4), and combreglucoside (5) were isolated from the stem bark of Combretum molle. Their structures were established mainly on the basis of 1D and 2D NMR spectral data. Compounds 1–3 exhibited more significant activity against carrageenan-induced paw edema in rat compared to compounds 4 and 5.Graphical abstractThe new triterpene saponin, β-d-glucopyranosyl 2α,3β,6β-trihydroxy-23-galloylolean-12-en-28-oate (1) together with the known combregenin (2), arjungenin (3), arjunglucoside I (4), and combreglucoside (5) were isolated from the stem bark of Combretum molle. Their structures were identified by interpretation of their spectral data, mainly ESIMS, 1D NMR (1H, 13C NMR, DEPT) and 2D NMR (COSY, HSQC and HMBC), and by comparison with the literature. Compounds 1–3 exhibited more significant anti-inflammatory activity against carrageenan-induced paw edema in rat compared to compounds 4 and 5.
Three artificial triterpenoids, (20R)-20,25-epoxy-dammaran-2-en-6α,12β-diol (1), (20R)-20,25-epoxy-3-methyl-28-nordammaran-2-en-6α,12β-diol (2) and isodehydroprotopanaxatriol (3), were isolated from an acidic hydrolysate of Panax ginseng C.A. Meyer, along with three known triterpenes, (20R)-panaxadiol (4), (20R)-panaxatriol (5) and oleanolic acid (6). Compounds 1–3 and 6 showed inhibitory activity against HIV-1 protease with IC50 of 10.5, 10.3, 12.3 and 6.3 μM, respectively. The results indicated that acid treatment of Ginseng extract could produce diverse structures with interesting bioactivity.Graphical abstractThree artificial triterpenoids were isolated along with three known ones, from an acidic hydrolysate of Panax ginseng. Four of them showed inhibitory activity on HIV protease.
Three xanthones, named cochinchinones E-G, together with 10 known xanthones and a known anthraquinone were isolated from the root, fruit and twigs of Cratoxylum cochinchinense. Their structures were characterized by spectroscopic methods. Some of the compounds had antibacterial and cytotoxic activities.Graphical abstractThree xanthones, named cochinchinones E-G, together with 10 known xanthones and a known anthraquinone were isolated from the root, fruit and twigs of Cratoxylum cochinchinense. Their structures were characterized by spectroscopic methods. Some of the compounds had antibacterial and cytotoxic activities.
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.Graphical abstract24(R)-Ethylcholest-6-ene-5α-ol-3-O-β-d-glucopyranoside (1), along with 11 known compounds (2–12) including aporphine alkaloids, diterpenes, a steroid glycoside and a flavonoid glycoside were isolated from the leaves of Nelumbo nucifera and evaluated for their antifungal, antimalarial and for cytotoxic activities. Antifungal activity was observed for (R)-roemerine (3) and antimalarial activity for (R)-roemerine (3) and N-methylasimilobine (5). Position C-1 and C-2 of aporphine alkaloids is crucial for antimalarial activity.
A galactomannoglucan (GMG) with an estimated weight-average molar mass of 1.5×105 was obtained from an aqueous extract of the mesocarp of fruits of Arecastrum romanzoffianum (Cham.) Becc. by fractionation by Sephacryl S-300 HR and Sephadex G-25. Chemical and spectroscopic studies indicated that GMG has a chain of (1→4)-linked β-d-mannopyranosyl residues, a chain of (1→3)-linked β-d-galactopyranosyl residues, a chain of (1→4)-linked α-d-glucopyranosyl residues, repeating units of β-d-galactopyranosyl-(1→4)-β-d-mannopyranosyl and β-d-mannopyranosyl-(1→4)-α-d-glucopyranosyl and terminal residues of d-galactopyranosyl and d-glucopyranosyl which comprised galactose, mannose and glucose in the molar ratio of 10:37:53. The polysaccharide exhibited significant antiinflammatory activity against carrageenan-induced mouse paw oedema.
A new xanthone, 3,4-dihydro-8,10,12-trihydroxy-2,2-dimethylpyrano[2,3-b]xanthen-11(2H)-one or butyraxanthone E (1), along with the known compounds 30-epi-cambogin (2), 1,7-dihydroxyxanthone (3) and 1,5-dihydroxyxanthone (4) were isolated from the roots of Pentadesma butyracea. Their structures were elucidated by spectroscopic means and comparison with published data. Their antiproliferative activities were evaluated against Drosophila S2 cells and two human cancer cell lines, THP-1 (leukemia) and HCT116 (colon cancer). Compounds 1 and 2 showed moderate antiproliferative activity against Drosophila S2 cells and the HCT116 cell line, respectively. Compound 2 was active against Drosophila S2 cells.
A novel isoflavan-4-ol (pumilanol), (rel)-3β-(2′-hydroxy-4′,5′-methylenedioxyphenyl)-6-methoxy-4α,7-dihydroxybenzo-3,4-dihydropyran (1) and two known flavonoids, tephrinone (2) and rotenone (3) together with lupeol and stigmasterol were isolated from the roots of Tephrosia pumila (Fabaceae) from a collection made in Andhra Pradesh, India. The structures of the compounds were determined by MS, 1D and 2D-NMR spectral analysis. Pumilanol (1) exhibited significant antiprotozoal activity against T. b. rhodensiense, T. cruzi and L. donovani with IC50 of 3.7, 3.35 and 17.2 μg/mL, respectively, but displayed high toxicity towards L-6 (IC50 of 17.12 μg/mL) rat skeletal myoblasts.Graphical abstractA novel isoflavan-4-ol (pumilanol), (rel)-3β-(2′-hydroxy-4′,5′-methylene dioxyphenyl)-6-methoxy-4α,7-dihydroxybenzo-3,4-dihydropyran (1) and two known flavonoids, tephrinone (2) and rotenone (3) together with lupeol and stigmasterol were isolated from the roots of Tephrosia pumila (Fabaceae). Pumilanol (1) exhibited significant antiprotozoal activity against T. b. rhodensiense, T. cruzi and L. donovani with IC50 of 3.7, 3.35 and 17.2 μg/mL, respectively, but displayed high toxicity towards L-6 cells (IC50 of 17.12 μg/mL).
Bioassay-guided fractionation of the EtOH extract of Artocarpus sepicanus Diels leaves has led to the isolation of a new geranyl flavanone (1), along with the known compounds, afzelechin-3-O-α-l-rhamnopyranoside and β-sitosterol glucoside. The structure of the new compound was established by UV, IR, HRESIMS, 1D and 2D NMR experiments. Antimicrobial testing of the three compounds indicated that 1 displayed a significant selective antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with IC50 and MIC values of 1.4 and 2.9μM, respectively.
Six known compounds, atranorin (1) and its derivatives methyl β-orcinol carboxylate (2) and methyl haematommate (3), the depsidones α-alectoronic acid (4) and α-collatolic acid (5), with its hydrolysis derivative β-collatolic acid (6), and a new compound, deoxycollatolic acid (7) have been isolated from the lichen Tephromela atra (Huds.) Hafellner (syn. Lecanora atra). The characterization of the new compound 7 was carried out by extensive NMR studies using COSY, HMQC, HMBC in addition to other spectroscopic methods. 1H NMR spectra recorded at low temperature showed β-collatolic acid (6) was corresponding to an equilibrium of conformers.Compounds 5 and 6 showed a better superoxide anion scavenging activity (IC50 = 463 and 122 μM, respectively) than quercetin (IC50 = 754 μM).Graphical abstractβ-Collatolic acid (6) along with a new compound deoxycollatolic acid (7) were isolated from the crustose lichen Tephromela atra. The complex equilibrium of collatolic acid derivatives was discussed according to the NMR data recorded at various temperatures (223–353 K).
The CH2Cl2 and MeOH extracts from leaves of Piper caldense were subjected to chromatographic separation procedures to afford the new prenylated benzoic acid, caldensinic acid (3-[(2′E,6′E,10′E)-11′-carboxy-3′,7′,15′-trimethylhexadeca-2′,6′,10′,14′-tetraenyl]-4,5-dihydroxybenzoic acid) whose structure was determined by spectral analysis, mainly NMR (1H, 13C, HSQC, HMBC) and ESI-MS. The natural compound and derivatives displayed antifungal activity against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum by direct bioautography.
Three novel polyisoprenylated benzophenones, semsinones A–C have been isolated from the stem bark of Garcinia semseii together with a known monocyclic triterpene, achilleol A. The structures of the new compounds have been determined by analysis of the spectroscopic data and comparison of the NMR data with those of the closely related compounds previously reported.Graphical abstractThree novel polyisoprenylated benzophenones, semsinones A–C (1–3) have been isolated from the stem bark of Garcinia semseii together with a known monocyclic triterpene, achilleol A. The structures of the new compounds were determined by analysis of spectroscopic data.
Three new benzylated glycosides, locoracemosides A, B and C (1–3) were isolated from the bark of the stem of Symplocos racemosa Roxb. Their structures were determined by spectroscopic and chemical evidences. They displayed in vitro inhibitory activity against α-chymotrypsin.Graphical abstractLocoracemosides A, B and C, three benzylated glycosides were isolated from the bark of the stem of Symplocos racemosa which displayed inhibitory potential against α-chymotrypsin enzyme.