Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

Identification and characterization of silver nanoparticles from Erythrina indica and its antioxidant and Uropathogenic antimicrobial properties.

The plant Erythrina indica comes under Fabaceae family, mainly used for used in traditional medicine as nervine sedative, antiepileptic, antiasthmatic, collyrium in opthalmia, antiseptic. Current study focused synthesize of silver nanoparticles (AgNPs) by E. indica leaf ethanol extract. The green-synthesized AgNPs underwent characterization using multiple analytical techniques, including UV-visible, FTIR, DLS, SEM, TEM, XRD, and EDX, and estimation of their antioxidant activity and antimicrobial activity. Phytochemical analysis identified alkaloids, tannins, saponins, flavonoids, and phenols as secondary metabolites. The Total Phenol Content (TPC) was determined to be 237.35 ± 2.02 mg GAE-1, indicating a substantial presence of phenolic compounds. The presence of AgNPs was verified through UV-Visible analysis at 420 nm, and FT-IR revealed characteristic phenolic functional groups. DLS analysis indicated a narrow size distribution (polydispersity index - PDI: 3.47%), with SEM revealing spherical AgNPs of approximately 20 nm. TEM showed homogeneous, highly polycrystalline AgNPs with lattice spacing at 0.297. XRD analysis demonstrated crystallinity and purity, with distinct reflection peaks corresponding to miller indices of JCPDS card no. 01 087 1473. In vitro, AgNPs exhibited robust antioxidant activity like; DPPH, ABTS, and H2O2, surpassing E. indica-assisted synthesis. ABTS assay indicated higher antioxidant activity (81.94 ± 0.05%) for AgNPs at 734 nm, while E. indica extraction showed 39.67 ± 0.07%. At 532 nm, both E. indica extraction (57.71 ± 0.11%) and AgNPs (37.41 ± 0.17%) exhibited H2O2 scavenging. Furthermore, AgNPs displayed significant antimicrobial properties, inhibiting Staphylococcus aureus (15.7 ± 0.12 mm) and Candida albicans (10.7 ± 0.17 mm) byfor the concentration of 80 µg/mL. Through the characterizations underscore of the potential of Erythrina indica-synthesized AgNPs, rich in polyphenolic compounds, for pharmacological, medical, biological applications and antipyretic properties.

Metabolomic study of the estrogenic and anti-osteoporotic potential of Erythrina bidwillii leaf.

Erythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and gas chromatography-mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8-oxoerythraline (2), (+)-erythrinine (3), (+)-erythraline (4) and 8-oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti-osteoporotic, anti-hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF-7 cell lines. An in silico study of the isolated metabolites revealed that (+)-erythrinine (3) and 8-oxoerythrinine (5) exhibited the highest affinity for ERα and ERß, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials.

Release of Bioactive Peptides from Erythrina edulis (Chachafruto) Proteins under Simulated Gastrointestinal Digestion.

The estimated and concerning rise in world population over the next few years and the consequent increase in food demand will lead to a deterioration in global food security. To avoid or reduce this world crisis, informed and empowered consumers are turning to sustainable and nutrient-rich foods that substitute animal products, also reducing their associated environmental impact. Moreover, due to the demonstrated influence of diet on the risk of high incidence and mortality of noncommunicable diseases, the current established food pattern is focused on the consumption of foods that have functionality for health. Among these new foods, traditional and underutilized plants are gaining interest as alternative protein sources providing nutritional and biological properties. In this work, the potential of Erythrina edulis (chachafruto) proteins as a source of multifunctional peptides after transit through the gastrointestinal tract has been demonstrated, with antioxidant and immunostimulating effects in both biochemical assays and cell culture. While low molecular weight peptides released during the digestive process were found to be responsible for protection against oxidative stress mediated by their radical scavenging activity, high molecular weight peptides exerted immunostimulating effects by upregulation of immunoresponse-associated biomarkers. The findings of this study support the promising role of chachafruto proteins as a new antioxidant and immunostimulatory ingredient for functional foods and nutraceuticals.

[Studies on the Isolation and Molecular Mechanisms of Bioactive Phytochemicals].

Studies on the isolation and molecular mechanisms of phytochemicals with anti-tumor or anti-inflammatory properties are important to developing new drugs for cancer and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. In the course of a study to screen bioactive isoflavones from Erythrina poeppigiana (Leguminosae), we isolated an isoflavone with potent apoptosis-inducing activity against human leukemia HL-60 cells. It was designated erypoegin K. The studies demonstrated an enantiomer, (S)-erypoegin K, displayed selective cytotoxic activity, was a novel inhibitor of topoisomerase II, and possessed anti-tumor activity both in vitro and in vivo. We identified other apoptosis-inducing isoflavones with the ability to inhibit glyoxalase I. Dimeric acridone alkaloids, carbazole alkaloids, and coumarin and quinoline derivatives-all obtained mainly from plants in the family Rutaceae-induced apoptosis of HL-60 cells via the production of reactive oxygen species and mitochondrial dysfunction. We also identified terpenoid coumarins, carbazole quinones, rotenoid derivatives, and quinolone alkaloids with anti-inflammatory activities. These compounds reduced nitric oxide (NO) production from RAW264.7 macrophage cells stimulated with lipopolysaccharides and interferon-γ. Some of the compounds displayed neuroprotective activity by reducing NO production. This review primarily describes our recent studies on erypoegin K, and other compounds with apoptosis-inducing and anti-inflammatory activities.

In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts.

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC50 concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH2Cl2 extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research.

(±) Erysectin A, a new isoprenylated isoflavone with a rare acetonyl group from Erythrina secundiflora Hassk.

(±) Erysectin A (1), a new isoprenylated isoflavone with a rare acetonyl group, along with 15 known compounds including eight isoprenylated isoflavones (2-9), two isoprenylated flavanones (10-11), three flavanones (12-14), a flavone (15), and a chalcone (16), was isolated from the twigs and leaves of Erythrina secundiflora Hassk. Their structures were identified based on their 1 D and 2 D NMR spectral data. All the compounds were isolated from this plant for the first time. Compound 1 showed moderate cytotoxicity on several cancer cell lines.[Formula: see text].

Flavonoids and other Non-alkaloidal Constituents of Genus Erythrina: Phytochemical Review.

BACKGROUND: Genus Erythrina belongs to family Fabaceae, which is widely distributed in tropical and subtropical areas. It has been used in both traditional herbal medicines and pharmacological applications. Original research articles and publications on the overview of alkaloids related to this genus are available, but a supportive systematic review account which highlighted phytochemical aspects of other types of secondary metabolites is currently insufficient. OBJECTIVE: With the utilization of data and information from SCI-Finder, Google Scholar, the Web of Science, Scopus, Science Direct, PubMed, Chemical Abstracts, ACS journals, Springer, Taylor Francis, Bentham Science and IOP Science, the reliable material sources of this systematic review paper were obtained from the literature published from the 1980s to now. CONCLUSION: A vast amount of data showed that the non-alkaloidal secondary metabolites were obtained from genus Erythrina with various classes of chemical structures. Herein, approximately five hundred constituents were isolated, comprising flavonoids, terpenoids, saponins, phytosterols, phenols, arylbenzofurans, coumarins, alcohols, ceramides, mono-sugars and fatty acid derivatives. In agreement with the previous phytochemical reports on the plants of the family Fabaceae, flavonoids reached a high amount in the plants of genus Erythrina. Numerous biological activity investigations such as anti-bacteria, anti-cancer, anti-virus using isolated compounds from Erythrina species suggested that secondary metabolites of Erythrina plants are now becoming the promising agents for drug developments.

Phytochemical and GCMS approaches to identify active constituents in Erythrina suberosa bark extract and evaluation of its therapeutic potency.

Humans rely on plants as a necessitous source of their food, energy, cosmetics and medicines, as medicinal plants are rich source of new therapeutically active compounds from decades. Current study was designed to separate and identify active constituents of Erythrina suberosa bark extract using phytochemical screening and gas chromatography and mass spectroscopy, respectively and evaluated their therapeutic activities. E. suberosa bark extract contained saponins, glycosides, alkaloids, tannins, terpenoids, phenols and 44 active compounds identified by phytochemical and gas chromatography and mass spectroscopic analysis. Therapeutic potentials of E. suberosa bark extract was evaluated by such as cytotoxicity, anti-inflammatory and antioxidant assay. Surprisingly, bark extract shows the concentration dependent cytotoxicity against human fibroblast malignant melanoma-144 cell lines and remarkably inhibited (15.18(plusmn;1.13%, at 400mg/ml) growth of cancer cells after 24 hours treatment. In addition, the E. suberosa bark extract also exhibited anti-inflammatory effect at higher doses (400mg/kg) and moderate antioxidant activity is also noticed through (2, 2-diphenyl-1-picrylhydrazyl radical) assay. These findings indicate that E. suberosa bark extract exhibited prominent anticancer and anti-inflammatory activities and might be serve as a potent therapeutic agent in future.

(S)-Erypoegin K, an isoflavone isolated from Erythrina poeppigiana, is a novel inhibitor of topoisomerase IIα: Induction of G2 phase arrest in human gastric cancer cells.

Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has a single chiral carbon in its structure and exists naturally as a racemic mixture. Our previous study showed (S)-erypoegin K selectively exhibits potent anti-proliferative and apoptosis-inducing activity against human leukemia HL-60 cells. To identify the target molecule of (S)-erypoegin K, we employed the human cancer cell panel analysis (termed JFCR39) coupled with a drug sensitivity database of pharmacologically well-characterized drugs for comparison using the COMPARE algorithm. (S)-erypoegin K exhibited a similar profile to that of etoposide, suggesting the molecular target for erypoegin K may be topoisomerase II (Topo II). Subsequent experiments using purified human Topo IIα established that the (S)-isomer selectively stabilizes the cleavage complex composed of double-stranded plasmid DNA and the enzyme. Moreover, (S)-erypoegin K inhibited decatenation of kinetoplast DNA. Molecular docking studies clearly indicated specific binding of the (S)-isomer to the active site of Topo IIα involving hydrogen bonds that help stabilize the cleavage complex. (S)-erypoegin K displayed potent cytotoxic activity against two human gastric cancer cells GCIY and MKN-1 with IC50 values of 0.270 and 0.327 µM, respectively, and induced enzyme activities of caspase 3 and 9. Cell cycle analysis showed marked cell cycle arrest at G2 phase in both cell lines. (S)-erypoegin K also displayed significant antitumor activity toward GCIY xenografted mice. The present study suggests (S)-erypoegin K acts as a Topo II inhibitor to block the G2/M transition of cancer cells.

Induction of enantio-selective apoptosis in human leukemia HL-60 cells by (S)-erypoegin K, an isoflavone isolated from Erythrina poeppigiana.

Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has potent apoptosis-inducing effect on human leukemia HL-60 cells. Erypoegin K has a chiral carbon at the C-2'' position of its furan ring and naturally occurs as a racemic mixture of (S)- and (R)-isomers. In the present study, we semi-synthesized (RS)-erypoegin K from genistein and separated the optical isomers by HPLC using a chiral column to characterize its apoptosis-inducing activity. Apoptotic cell death was assessed by analyzing caspase-3 and caspase-9 activation, nuclear fragmentation, and genomic DNA ladder formation. (S)-erypoegin K showed exclusive anti-proliferative and apoptosis-inducing activity, with an IC50 value of 90 nM, about 50% lower than that of its racemic mixture (175 nM). By contrast, no apoptosis-inducing activity was shown by the (R)-isomer. In addition, methylglyoxal accumulation in the culture medium was observed only in cells treated with (S)-erypoegin K. These results demonstrated that (S)-erypoegin K is a unique bioactive component that has potent apoptosis-inducing activity on HL-60 cells.

Excelsanone, a new isoflavonoid from Erythrina excelsa (Fabaceae), with in vitro antioxidant and in vitro cytotoxic effects on prostate cancer cells lines.

A new isoflavonoid, excelsanone (2), was isolated from the ethyl acetate extract of Erythrina excelsa stem bark, together with three known compounds namely 6,8-diprenylgenistein (3), ß-sitosterol (1) and sitosteryl-ß-D-glucopyranoside (4). Their structures were elucidated using spectroscopic methods (HR-ESI-MS, NMR and IR) and by comparison with some literature data. The antioxidant activity of crude extracts and two isolated compounds was evaluated using free radical scavenging (DPPH) and Ferric Reducing Ability Power (FRAP) methods with catechin as standard. The results of the radical scavenging activity showed that excelsanone (2) has a moderate potential with an IC50 of 1.31 mg/ml. The cytotoxicity of compounds 2 and 3 as well as the ethyl acetate extract was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in two prostate cancer cell lines (DU145 and PC3). Excelsanone (2) induced a greater cytotoxicity in all tested cell lines, with a significant inhibition of DU145 cells growth in a concentration-dependent manner.

Alkaloids of genus Erythrina: An updated review.

Genus Erythrina (Fabaceae) comprises several species, which are widely distributed in tropical and subtropical regions of the world. The plants of this genus exhibited significant role in traditional medicine targeting different diseases. Alkaloids and flavonoids were reported as the chief bioactive constituents of this genus with a wide range of biological activities. About 143 alkaloids were isolated from Erythrina sp. Anticonvulsant, anxiolytic, curare-like activity, insecticidal and cytotoxic activities were reported for Erythrina sp. alkaloids. The present work is an overview of the isolated alkaloids from Erythrina sp. with their reported biological activities.[Figure: see text]Abbreviations: CHCl3: Chloroform; CNS: Central nervous system; DCM: Methylene chloride; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; E.: Erythrina; ERα/ß: Estrogen receptors α/ß; EtOAc: Ethyl acetate; EtOH: Ethanol; Hep-G2: Human liver carcinoma cell lines; HIV: Human immunodeficiency virus; HL-60: Human promyelocytic leukemia cells; K-562: Human immortalized myelogenous leukemia cell line; LPS: Lipopolysaccharide; MeOH: Methanol; MOLT-4: Acute lymphoblastic leukemia cell line; nAChRs: nicotinic acetylcholine receptors; NO: Nitric oxide; NREM: non-rapid eye movement; Pet. ether: Petroleum ether; RBA: Receptor binder affinity; TRAIL: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand.

Essential oil extracted from erythrina corallodendron L. leaves inhibits the proliferation, migration, and invasion of breast cancer cells.

Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.

Hepatoprotective activity of Erythrina × neillii leaf extract and characterization of its phytoconstituents.

BACKGROUND: Natural antioxidants and anti-inflammatory agents have the ability to restore normal balance to destructed liver cells. The genus Erythrina has attracted attention for its broad spectrum of physiological activities and its rich polyphenolic and alkaloid contents. HYPOTHESIS/PURPOSE: The major phytoconstituents of Erythrina × neillii, an ornamental coral tree and a hybrid between E. herbacea and E. humeana that was not previously studied, were investigated. The hepatoprotective effect and underlying mechanisms were also assessed. STUDY DESIGN AND METHODS: The main phytoconstituents in the different fractions of the alcoholic leaf extract (dichloromethane and ethyl acetate) were identified using high resolution high-performance liquid chromatography coupled with mass spectrometry (HR-HPLC-MS-MS) based on the fragmentation pattern and molecular formula of the identified compounds and on previous literature. In addition, the hepatoprotective, anti-inflammatory and antioxidant activities of three doses of E. × neillii alcoholic leaf extract (100, 250, 500 mg/kg) were investigated in methotrexate (MTX)-intoxicated rats and were compared with those of silymarin-treated rats. Liver function parameters were obtained, and a histopathological study was performed. In addition, the anti-inflammatory mediators and the antioxidant system in the liver tissues were assessed. RESULTS: The dichloromethane extract revealed an abundance of alkaloids (25), in addition to tentatively identifying flavone (1), flavanone (1) and three fatty acids. Additionally, thirty-six compounds belonging to different classes of phytoconstituents with a predominance of flavonoids (21), O/C-flavone and flavonol glycosides, followed by alkaloids (9), fatty acids (4) and (2), and phenolic glycoside were identified in the ethyl acetate extract. Compared with MTX, alcoholic leaf extract (500 mg/kg) ameliorated the MTX-induced alterations by improving several biochemical marker levels, fighting oxidative stress in serum and liver tissues, and decreasing inflammatory mediators; this finding was further confirmed by the histopathological study. CONCLUSION: This study reveals E. × neillii, a rich source of flavonoids and alkaloids, which could be further exploited to provide a promising and safe antihepatotoxic agent source.

Profiling the N-Glycan Composition of IgG with Lectins and Capillary Nanogel Electrophoresis.

Glycosylated human IgG contains fucosylated biantennary N-glycans with different modifications including N-acetylglucosamine, which bisects the mannose core. Although only a limited number of IgG N-glycan structures are possible, human IgG N-glycans are predominantly biantennary and fucosylated and contain varying levels of α2-6-linked sialic acid, galactose, and bisected N-acetylglucosamine. Monitoring the relative abundance of bisecting N-acetylglucosamine is relevant to physiological processes. A rapid, inexpensive, and automated method is used to successfully profile N-linked IgG glycans and is suitable to distinguish differences in bisection, galactosylation, and sialylation in N-glycans derived from different sources of human IgG. The separation is facilitated with self-assembled nanogels that also contain a single stationary zone of lectin. When the lectin specificity matches the N-glycan, the peak disappears from the electropherogram, identifying the N-glycan structure. The nanogel electrophoresis generates separation efficiencies of 500 000 plates and resolves the positional isomers of monogalactosylated biantennary N-glycan and the monogalactosylated bisected N-glycan. Aleuria aurantia lectin, Erythrina cristagalli lectin (ECL), Sambucus nigra lectin, and Phaseolus vulgaris Erythroagglutinin (PHA-E) are used to identify fucose, galactose, α2-6-linked sialic acid, and bisected N-acetylglucosamine, respectively. Although PHA-E lectin has a strong binding affinity for bisected N-glycans that also contain a terminal galactose on the α1-6-linked mannose branch, this lectin has lower affinity for N-glycans containing terminal galactose and for agalactosylated bisected biantennary N-glycans. The lower affinity to these motifs is observed in the electropherograms as a change in peak width, which when used in conjunction with the results from the ECL lectin authenticates the composition of the agalactosylated bisected biantennary N-glycan. For runs performed at 17 °C, the precision in migration time and peak area was less than or equal to 0.08 and 4% relative standard deviation, respectively. The method is compatible with electrokinetic and hydrodynamic injections, with detection limits of 70 and 300 pM, respectively.

Novel antioxidant peptides obtained by alcalase hydrolysis of Erythrina edulis (pajuro) protein.

BACKGROUND: Oxidative reactions are responsible for the changes in quality during food processing and storage. Oxidative stress is also involved in multiple chronic diseases, such as cardiovascular and neurodegenerative disorders, diabetes, cancer, and aging. The consumption of dietary antioxidants has been demonstrated to help to reduce the oxidative damage in both the human body and food systems. In this study, the potential of Erythrina edulis (pajuro) protein as source of antioxidant peptides was evaluated. RESULTS: Pajuro protein concentrate hydrolyzed by alcalase for 120 min showed potent ABTS·+ and peroxyl radical scavenging activity with Trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) values of 1.37 ± 0.09 µmol TE mg-1 peptide and 2.83 ± 0.07 µmol TE mg-1 peptide, respectively. Fractionation of the hydrolyzate to small peptides resulted in increased antioxidant activity. De novo sequencing of most active fractions collected by chromatographic analysis enabled 30 novel peptides to be identified. Of these, ten were synthesized and their radical activity evaluated, demonstrating their relevant contribution to the antioxidant effects observed for pajuro protein hydrolyzate. CONCLUSIONS: The sequences identified represent an important advance in the molecular characterization of the pajuro protein, demonstrating its potential as a source of antioxidant peptides for food and nutraceutical applications. © 2018 Society of Chemical Industry.

An Update of Erythrinan Alkaloids and Their Pharmacological Activities.

The period of the past 5 years has witnessed a remarkable increase in all of the number, structural variety, and complexity of erythrinan alkaloids reported. This structural diversity seems to be most pronounced in the alkaloids reported from the two species Erythrina arborescens and Erythrina variegata. Between them, work-up of these taxa yielded new polymeric (dimeric and trimeric) erythrinan alkaloids, a first example in one case where a normal 6,5,6,6-membered indoloisoquinoline spirocylic core has rearranged to a spiro-fused 6,5,7,6-skeleton. Furthermore, erythrinan alkaloids with a fifth ring containing a 2H-imidazole functionality were also reported for the first time, together with some new structures having an unusual substitution and with functionalities at positions C-3 and C-7 of the erythrinan core. This contribution has included 40 more erythrinan alkaloids that are either new or were omitted in the most recent major reviews on the same topic, leading to a total of 154 known erythrinan alkaloids to date. There are a few cases where the structures of the new alkaloids are contestable due to insufficient data having been obtained on isolation. To facilitate easier reference and identification, all structures having a common core have been placed in the same table or figure in this chapter.The reported pharmacological activities of the new and known erythrinan alkaloids documented have shown a considerable bias towards central nervous system and related activities. Other prominent activities that have been reported are antifeedant, insecticidal, cytotoxic, antiprotozoal, anti-inflammatory, antioxidant, antifungal, and antiviral effects. Erythrinan alkaloids generally seem to lack antibacterial activity. Several new polymeric alkaloids were found to lack cytotoxicity against a number of human cancer cell lines, although two of them showed moderate aphicidal activity and one exhibited weak to moderate acetylcholinesterase inhibition. The biological activity of erythrinan alkaloids seems to be influenced by basic substructural requirements, such as a conjugated diene (Δ1,2, Δ6,7) system and is modulated by the presence (or absence) of other groups in rings A, B, C, and D of the erythrinan core. The erythrinan core may provide potential leads to structures that eventually may be useful therapeutically.In recent years, a number of stereoselective chemical synthesis methods have been applied towards the erythinan alkaloids, and these are described in this contribution.

Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells.

Erypoegin K is an isoflavone isolated from the stem bark of Erythrina poeppigiana. It contains a furan group at the A-ring of the core isoflavone structure and can inhibit the activity of glyoxalase I, an enzyme that catalyzes the detoxification of methylglyoxal (MG), a by-product of glycolysis. In the present study, we found that erypoegin K has a potent cytotoxic effect on human leukemia HL-60 cells. Its cytotoxic effect was much stronger than that of a known glyoxalase I inhibitor S-p-bromobenzylglutathione cyclopentyl diester. Conversely, erypoegin K demonstrated weak cytotoxicity toward normal human peripheral lymphocytes. The treatment of HL-60 cells with erypoegin K significantly induced caspase-3 activity, whereas the pretreatment of the cells with caspase-3 inhibitor suppressed erypoegin K-induced cell death. Furthermore, nuclear condensation and apoptotic genome DNA fragmentation were observed in erypoegin K-treated HL-60 cells. These results indicated that the observed cell death was mediated by apoptosis. In addition, the toxic compound MG was highly accumulated in the culture medium of erypoegin K-treated HL-60 cells, suggesting that cell apoptosis was triggered by extracellular MG. The present study showed that erypoegin K has a potent apoptosis-inducing effect on cancerous cell lines, such as HL-60.

A New Erythrinan Alkaloid Glycoside from the Seeds of Erythrina crista-galli.

A new Erythrina alkaloid glycoside, named erythraline-11ß-O-glucopyranoside, was isolated from the seeds of Erythrina crista-galli L., together with five known Erythrina alkaloids and an indole alkaloid. The structure of the new alkaloid glycoside was elucidated by spectroscopic methods, and all of the compounds were evaluated for their antiviral activity against tobacco mosaic virus.